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by Paramananda Barman February 8, 2017

Photo: Siddharth Kankaria 

A recent report by the World Health Organization estimates that about two million deaths occur every year due to tuberculosis (TB). An alarming dimension to this problem is the fact that some strains of Mycobacterium tuberculosis (Mtb), the causative agent of TB, have developed resistance to some antibiotics used to kill them, leading to the emergence of ‘drug resistant TB’ and causing a global threat. Drug resistance is a way by which bacteria respond to the drug stress they face. Due to improper and irregular use of antibiotics by patients, not all bacteria may be killed, leading to the emergence of drug resistant strains that survive even when further doses of the drug are administered. Now, a team of researchers at the Indian Institute of Science, Bangalore, led by Prof. Nagasuma Chandra and Prof. Amit Singh, have explored the mechanism behind the development of resistance to a front-line anti-tubercular drug called isoniazid, used widely in the clinic.

The researchers evolved a drug resistant strain of a model species in the laboratory and used a combined approach involving genomics, computational modeling, systems biology, genetic assays, and chemical and sensor based tools to study the mechanisms behind drug resistance. Based on the results, the researchers have, for the first time, reported a complete landscape of the genetic and phenotypic changes occurring in the model organism during the evolution of drug-resistance. They observed that, in addition to genetic changes, the bacteria acquired new characteristics in its transition from a ‘drug-sensitive’ strain to a ‘drug-resistant’ strain. Conventional antibiotics used to treat TB ultimately cause oxidative stress in Mtb, leading to its death. Their observations showed that the drug resistant strain developed an ability to respond to the oxidative stress by switching on its antioxidant machinery and thereby neutralizing the oxidative stress caused by the antibiotic. This was observed both in the model system and in the virulent strain of Mtb.

So how do we overcome the problem of drug resistance? The researchers have identified an Achilles’ heel in the drug-resistant strains - vulnerable spots that exist despite the overall fitness. They hypothesized that targeting the bacterial antioxidant mechanisms may kill the resistant bacilli and identified a new class of drugs including ebselen, vancomycin and phenylarsine oxide that inhibit the bacterial antioxidant responses. They found that when any of these drugs were used in combination with isoniazid, the drug to which the strain is resistant to, the efficacy of the drug in killing the resistant strains was much higher than when these drugs were used individually.

Further experiments confirmed that the combination of isoniazid with other antibiotics indeed reversed the resistance and rescued sensitivity of the strain to the initial drug. The researchers also observed that the combination increased the potency of isoniazid several fold in drug-sensitive and drug-resistant strains, implying that even when there is no drug resistance, the combination can lower the amount of isoniazid required, thus reducing the chances of side effects. Among the new drug combinations studied, ebselen and vancomycin, in combination with isoniazid, were found to be the most promising candidates for combating drug resistant TB.

The researchers believe that this study has opened new avenues of research on drug-resistant TB, which can further be exploited to make new strategies for targeting TB infections. “Our work has identified new compounds, which when combined with an existing anti-TB drug, can rescue drug sensitivity and enhance killing of the drug-resistant mycobacteria. Of these compounds, vancomycin, is already in use for treating other bacterial infections. Hence, we propose that this can be easily explored for the treatment of drug-resistant TB infection too.  We are currently testing these combinations in animal models of TB infection”, say Profs. Chandra and Singh on their future plan.

Tag: CIDRBiochemistrymicrobiologycomputational biologyMycobacterium TuberculosisDrug resistance
by Madhura February 7, 2017

Photo: Siddharth Kankaria

Many lifesaving medical devices such as urinary catheters, pacemakers, intrauterine devices and voice prosthesis, which are usually inserted into some part of the body, are plagued by a common problem – ‘bacterial biofilms’. These ‘biofilms’ grow on the surfaces of these devices and may cause infections. They are harder to treat than individual bacteria and need about 1000 – 10000 times stronger dose of antibiotics. But this may no longer be the case, as a group of scientists led by Prof. Dipshikha Chakravortty and Prof. Jagadeesh Gopalan from the Indian Institute of Science, Bangalore, have found a novel method to fight biofilm infections.

Bacterial biofilms are formed by communities of bacteria, which adhere to a surface as a thin but strong layer, usually embedded in a mucilaginous polymer material that they secrete around themselves. This layer defends the bacteria from antibiotics, making them highly resistant. Bacterial biofilms are associated with infectious diseases like inflammation and tissue damage. While biofilm formation can be prevented to a certain extent by sterilizing the devices being inserted, devices like urinary catheters have a high chance of being infected since they are often exposed to contamination, leading to urinary tract infections.

Studies have shown that these bacteria remain resistant to antibiotics only as long as they are ensconced in the polymer layer formed in the biofilm. Once the layer is destroyed, these bacteria can be killed using much lower concentrations of antibiotics. Scientists at IISc have, for the first time, discovered that shock waves could be used to aid the action of antibiotics by disrupting the biofilm. Shockwaves are sharp, transient changes of pressure in a medium, caused by events such as explosions, or when a particle moves faster than the speed of sound. When used in a controlled manner, shockwaves can be used in delivering vaccines and drugs, crushing kidney stones and healing wounds.

“We have been successful in targeting different biofilms that may occur in different disease conditions - from lung infections to infections in urinary catheters. Shockwaves have shown great potential in disrupting these biofilms, even inside the body, making them more susceptible to antibiotics. Thus, shockwaves could be the future to treat biofilm infections”, says Akshay Date, a PhD scholar who worked on the project.

The researchers of the study considered three kinds of bacteria – P. aeruginosa, S. aureus and Salmonella, all of which are known to be associated with biofilms. They mimicked the conditions of a urinary catheter by growing these bacteria in actual urinary catheters filled with sterilized human and bovine urine. The sterilization was to ensure no external bacteria contamination occurred. They then treated the bacterial biofilm on the catheter with only antibiotic, only shockwaves, and a combination of both. They found that the shockwaves did indeed disrupt the bacterial biofilm, formed by all three kinds of bacteria. However, the combination of shockwaves and antibiotics succeeded in making the bacteria 100 – 1000 times more sensitive to the antibiotic ciprofloxacin.

The researchers also tested their methods to treat biofilm infections on devices that are always inside the body, unlike catheters that can be removed.  Using mice as a model, they tested their methods on mice infected with P. aeruginosa, which causes lung infection by forming biofilms and then treated the mice with antibiotic, shockwaves and a combination of both. They observed that the combined treatment fared significantly better. They also tested the effectiveness of their treatment method on S. aureus, a well-known cause of hospital-acquired infections, and found similar results.

While many studies and clinical trials are needed before this treatment becomes common, shock waves combined with antibiotic therapy shows a promising treatment for biofilm infections.

Tag: Bacteriabiofilmsbiomedical devicessterilizationshockwavesappplicationMCBDepartment of Aerospace Engineering
by Manohar February 4, 2017

Photo: Siddharth Kankaria

If you just relished a cup of yogurt or a platter of cheese, its time to thank the cook – bacteria! Yes, these microorganisms cook up the magic by converting the lactose in milk into lactic acid, thus giving a relishing taste. However, bacteria are often associated with diseases and despair they bring about – think of tuberculosis or ulcers – and are despised. What if, the same bacteria that we despise, are actually helpful in curing yet another serious and often life threatening disease like cancer? Sounds impossible? It is a little known fact that, at least in some cases of bacteria, we have been doing just that for the past 200 years with appropriate reprisals en route!

The first documented evidence of using bacterial therapy against cancer was in 1813, when it was observed that tumours started regressing in a patient suffering from gas gangrene, an infection caused by the bacterium Clostridium. Soon after, William Coley, a physician, came up with reproducible therapeutic efforts in treating patients with sarcomas. He treated cancer patients with a concoction of heat killed Streptococcus pyogenes and Serratia marcescens, known as Coley’s toxin. This discovery opened up a new field, called immunotherapy in cancer, where different strains of bacteria are used to successfully treat cancers like sarcomas, carcinomas, lymphomas, etc.

“In spite of several pre-clinical successes with different bacteria, therapeutic efficacy has not always been translated into human studies”, says Prof. Dipankar Nandi from the Department of Biochemistry and Centre for Infectious Disease Research, Indian Institute of Science, reiterating the distance this path-breaking alternative needs to go. Prof. Nandi and his team have worked on the effectiveness of Mycobacteruim indicus pranii, a harmless bacteria, in the treatment of different types of cancers. Interestingly, Mycobacteruim indicus pranii was first isolated by Prof. Gursaran Pran Talwar from the National Institute of Immunology, New Delhi. The name “indicus” comes from India, “pra” from his middle name and “nii” come from the name of the institute that he founded. Mycobacteruim indicus pranii, after undergoing extensive clinical trials, is approved for use in the treatment of leprosy patients along with chemotherapeutic drugs.

The modus operandi of the bacterial warriors

Conventional cancer therapies such as chemotherapy and radiotherapy are often characterized by the lack of tumour specificity, increased resistance of tumours to drugs, failure to detect metastases and undesirable side effects. Using bacteria, on the other hand, could be a ‘natural’, yet effective way of treatment without these undesired drawbacks.

But how do bacteria fight against tumours? The answer lies in the environment the tumour creates during its growth. A tumour, by definition, is a mass of cells that have divided in an uncontrolled, abnormal manner without respecting the normal boundaries. Bacteria are known to modulate our immune defence system and strengthen it to fight against tumour cells. Bacteria activate our immune systems and provide an environment for the production of T cells, a type of lymphocyte, that displays greater ability to specifically recognize and act against tumour cells.

For example, intra-dermal injection of Mycobacterium indicus prannii induces our immune cells to release chemicals called cytokines that recruit other cells to attack and kill tumour cells. Prof. Nandi’s lab has extensively researched into the mechanisms employed by Mycobacterium indicus pranii bacteria that fight against cancer. “Our research has shown that heat killed Mycobacterium indicus pranii, injected intra-dermally, induces anti-tumour T cells which lowers the growth of tumours”, comments Prof. Nandi.

The warriors in the field

Like MIP, there are a variety of bacterial warriors that work against different type of cancers. Some studies have focused on using Bacillus Calmette Guerin (BCG), a well-known bacterium used to vaccinate against tuberculosis. Often, BCG is the first vaccine received by babies as it is effective against tuberculosis. In fact, the only Food and Drug Administration (FDA) approved bacterial therapy against cancer uses live BCG. “It works as an immune stimulator against non-muscle invasive bladder cancer and is known for its demonstrated superiority over the drug doxorubicin”, explains Prof. Nandi. Although BCG is very effective against bladder cancer, it is known to cause significant immune toxicity.

In the tug of war between safety concerns and effectiveness, Mycobacterium indicus pranni stands out as a non-pathogenic and saprophytic bacterium. Unlike BCG, it can be used after being killed by heat and is still capable of all immunological responses. In some cases or conditions where MIP is not effective, a combination therapy with a drug called cyclophosphamide, has been found to be immensely effective.

Safety concerns and the future roadmap

Would it be safe to deliberately infect a patient with potentially disease causing bacteria? “Safety concerns do exist in cancer treatments”, admits Prof. Nandi. “For example, a major concern for the full exploitation of some bacteria in cancer treatment is their immunogenic properties which induce septic shock. Often, genetically engineered, less virulent strains of these bacteria have been developed by deleting their genes for pathogenicity”, he adds.

In the face of limitations of conventional cancer therapies and their side effects, bacterial therapy has the potential to turn into a cutting edge therapeutic approach against cancer and also improving the lives of cancer patients. Studying bacterial-induced immune responses could be an area for further and deeper clinical investigations and may increase our understanding of host immune network. “It is likely that more and more bacteria will be evaluated for their anti-cancer therapeutic efficacy and may pass through the clinical trials in the near future”, signs off Prof. Nandi with a hope for the future of immunotherapy. 

Tag: cancerimmunotherapymycobacteriumvaccinesBCGBacteria
by Dennis CJ February 3, 2017

Photo: Kishalay De / Undergraduate Department, IISc

Indian astronomers have detected microstructure emissions from a millisecond pulsar for the first time. Millisecond pulsars (MSP) are highly magnetized, rapidly rotating neutron stars that take as little as one-thousandth to one-hundredth of a second to rotate about its axis once. In a recently published study, scientists from the Department of Physics at the Indian Institute of Science (IISc) and the National Centre for Radio Astrophysics (NCRA), Tata Institute for Fundamental Research (TIFR), have discovered these microstructure emissions using the Giant Metrewave Radio Telescope (GMRT), an array of thirty antennae scanning the sky for radio sources. They are now uncovering the processes that produce these microstructure emissions. While similar emissions had been discovered from more slowly rotating pulsars, this is the first time they have been discovered coming from millisecond pulsars.

“Pulsars rotate at the rate of about a few tens of rotations per second, and emit a beam of radiation along their magnetic axis. When this beam crosses the line of sight of an observer on Earth, this radiation can produce periodic pulses, pretty much like how a light house creates a periodic flash when viewed from a distance”, says Mr. Kishalay De, an undergraduate at the Department of Physics, IISc, at the time of the study.  “If these neutron stars do not significantly interact with any other stars in their environment, they gradually slow down over time, giving rise to normal period pulsars, which typically have rotation periods of about a few tenths of a second to a few seconds. However, a significant fraction of these stars have nearby companion stars from which they gravitationally pull material onto their surface. As the material is pulled into the star, it spins up the rotating star, like a string pulling a spinning top, and gives rise to millisecond pulsars, which can rotate up to a few hundred times per second”, he adds.

While observing single pulses from normal period pulsars, researchers have long observed rapid periodic fluctuations within them, but did not understand their origin. Since the time scales of these fluctuations were of the order of about a few hundred microseconds, they came to be known as microstructures. But when scientists began looking for these microstructures in emission from MSPs, they did not find them, suggesting an absence of such structures within the pulses from a MSP, which could have important consequences for our understanding of microstructure emission.

For the current study, researchers made use of the high sensitivity of the Giant Meterwave Radio Telescope (GMRT), located near Pune, to radio waves with wavelength of about a metre. “The large collecting area of the telescope allows one to conduct very detailed studies of faint pulsars at low frequencies, which are otherwise impossible with almost all the other telescopes on Earth. Pulsars are also intrinsically brighter when viewed with low frequency radio waves, making the GMRT an ideal instrument for studying a variety of interesting phenomena in these sources”, remarks Mr De. The GMRT has been in operation since 2001. It is made of an array of thirty fully steerable, parabolic radio telescopes and can investigate a variety of radio sources like pulsars, neutron stars and other extragalactic radio sources.   

Although the current study does not identify the mechanisms behind microstructure emissions, it puts constraints on the possible reasons for the existence of such microstructures. With the GMRT undergoing a major upgrade, scientists will be able to further probe the mysteries behind pulsar emissions in greater detail. “These features could potentially be produced by the fundamental emitting entities responsible for pulsar radio emission, or be manifestations of physical processes associated with them. Hence, it is very important to study these features in detail, to shed light on the still elusive pulsar emission mechanism”, concludes Mr. De.

Tag: GMRTtelescopemillisceond pulsarsNCRATIFRAstronomy
by Savitha Sekhar Nair January 24, 2017

Prof. Raghavan Varadarajan, MBU, IIScProf. Raghavan Varadarajan, MBU, IISc

“Research is to see what everybody has seen and think what nobody has thought.

– Albert Szent-Györgyi [Nobel Prize in Physiology/ Medicine, 1937]

Genetic research is at a colossal high today, and although we know a lot about our genes, the roles of more than 30% of the functional genes in the human body are not really understood. This number can be even lower for other members of the biotic world.  Studies to determine gene function involve combinations of various experimental methods at biochemical, cellular, and organismal levels. One such method, that is popularly employed, uses temperature-sensitive mutant genes that behave differently at different temperatures. The process of identifying and generating mutated genes, however, is laborious, time-consuming and relies heavily on chance. It is at this juncture that Prof. Raghavan Varadarajan and his team from the Molecular Biophysics Unit, Indian Institute of Science, Bangalore, suggest an innovative, yet fairly straightforward, technique to study gene functionality, which would make one wonder how no one thought of this earlier!

Most of the ‘functional’ genes in our body function by serving as codes for the machinery inside our cells to produce specific proteins, each of which, in turn, have their own biological roles. Simply put, the function of most genes is the function of the protein that it codes for. So, how would one go about figuring out the role of a particular gene, especially when there is minimal knowledge of the encoded protein product? For organisms that do not maintain a constant body temperature, the use of temperature-sensitive mutations is a classical approach, where combinations of heat and cold-sensitive mutant genes are employed to decipher the role of various genes at different stages of an organism’s life.

The strategy generally involves mutating a particular gene such that its protein product can function normally at regular temperatures, but less efficiently at higher or lower temperatures, depending on the technique employed. For instance, if, bacterial cells — whose original ‘gene of unknown function’ is replaced with a mutated heat-sensitive copy of the same gene — can divide at regular temperatures but not at a higher temperature, one could conclude that the mutated gene plays a major role in bacterial cell division. In contrast, to heat-sensitive mutants, the molecular basis for cold-sensitive mutants is poorly understood and there exists no fool-proof method of successfully generating cold-sensitive mutants for a gene of interest. Hence these are often difficult to isolate.  Now, for the first time, Prof. Varadarajan and his team in collaboration with Prof K VijayRaghavan, have devised a straightforward method to generate cold-sensitive mutants of any gene that one might wish to study. Their procedure utilises computer programs to predict the regions of a particular gene that could be mutated to yield a protein product that is destabilized relative to the wild-type (unmutated) gene. Ideally, this ‘unstable protein’ would be less active at all temperatures when compared to the original, non-mutated one, but not completely inactive. After confirming the computer-generated predictions using live model organisms, the mutated gene is transferred into the test organism under the control of a heat-inducible promoter (HIP) that regulates protein production and can be controlled using temperature. When partnered with the mutated gene, these special promoters result in higher production of the protein at high temperatures and lower production at cold temperatures.

At high temperatures, the researchers observed that HIP orchestrated high protein production from the mutated gene. Even though the protein generated was unstable, the test organism could still function normally. However, at low temperatures, there is significantly less mutant protein produced due to the suboptimal functionality of HIP. Here, the organism displays a striking malfunction with respect to some observable trait, providing the researchers with a clue to the gene’s function. Using this method, the researchers successfully established cold-sensitive mutant strains of bacteria and yeast and could also transfer the mutant gene from yeast to fruit flies and still get it to function as desired, in a cold-sensitive fashion.

This study, apart from providing a useful tool in the lab, also offers a plausible explanation for how certain proteins in the cell purport as being cold sensitive. “It’s not that the protein has magically become inactive at lower temperatures”, explains Prof. Varadarajan, “it’s just that, at cold temperatures, the lower expression combined with the intrinsic instability of the mutant leads to an insufficient amount of functional protein.” Although researchers have previously established cold-sensitive mutants in their labs, a molecular rationale of this behaviour was previously lacking.

It is straightforward to generate mutants with lowered activity and HIP’s are also commonly used. However, combining these known concepts to generate cold-sensitive mutants is novel and can ultimately serve as an extremely valuable tool in the elucidation of gene function.

Tag: cold-sensitivephenotypesmolecular biologygene functionMutationgeneticsMBUNCBS
by Manohar January 19, 2017

Photo: Siddharth Kankaria

In the movie “Terminator: The Rise of Machines”, the character Terminatrix manipulates the Cyborgs tweaking them to work against humans and to her own advantage. Now, scientists have discovered that some strains of bacteria could do the same to some of our cells. Mycobacterium tuberculosis, the bacterium that causes tuberculosis, is one such. It manipulates the macrophages, a type of white blood cell that hunts and engulfs invading pathogens, to act as bacterial reservoirs and provide a survival niche. This niche not only provides the bacteria with nutrients, but also helps evade the normal immune response. In a recent study, a team of scientists from the Indian Institute of Science, Bangalore, has explored the mechanism behind the manipulation of macrophages by this bacteria.

Macrophages scout for foreign pathogens and engulf them, providing us with innate immunity. However, when specific strains of Mycobacterium infect these macrophages, they reprogram these cells to act as safe havens and to obtain nourishment from them. These modified macrophages are called Foamy Macrophages (FM) and are found in the granulomas of the lungs of infected individuals. “ Unlike other bacteria, Mycobacterium tuberculosis is not explicitly pathogenic, but it can lie dormant. Even today, it is one of the most dreaded pathogens with 6.1 million individuals newly infected with TB and 1.4 million dead due to the disease in 2015 alone. Thus, it is not surprising that this bacterium uses all means available at its disposal to manipulate the host environment”, explains Ms. Kasturi Mahadik, a research scholar at the Department of Microbiology and Cell Biology, IISc.

The researchers have worked out the molecular mechanism involved in the generation of Foamy Macrophages. The elucidation of this pathway could generate new and effective targets for drug development to cure tuberculosis. The study found that the bacterium interacts with a receptor found on the membrane of macrophages called TLR2 (Toll-like receptor). These receptors recognize foreign substances and pass on appropriate signals to the cells of the immune system through one of the signaling pathways called NOTCH1signaling pathway. “While viruses are legendary host modifiers, bacteria have been known to manipulate the host epigenetic machinery - host genes involved in cell cycle progression, cell ageing, survival, inflammation and immunity being important targets for such epigenetic control. Study of mycobacteria modulating the host epigenome is now gaining increasing recognition”, remarks Ms, Mahadik on the importance of the study.

Signaling pathways govern basic activities of cells and co-ordinate cell actions by allowing them to sense or perceive changes in their microenvironment and bring about necessary changes in activities like gene expression. The signal from outside of the cells is transmitted via a chain of mediators, the end point of which may culminate in the expression of certain genes, whose products are required to respond to the changes in the microenvironment.

Foamy Macrophages contain lipid bodies that provide nutrients and anti-inflammatory mediators to help the bacteria evade our normal immune response. Genes involved in lipid biosynthesis and lipid droplet synthesis are “regulated” or “turned on” for the purpose. Conventionally, gene regulation is brought about by a protein acting as an activator or a repressor of gene function.

The study found that either condensing or relaxing a chromosome regulates the genes required for the generation of Foamy Macrophages. Genes reside on chromosomes, and when chromosomes tightly coil up, they are not free to be transcribed and are therefore switched off. On the other hand, a relaxed and free chromosome can be bound by positive activators, which assist in gene expression and can be switched on. The DNA in the chromosome is wound around proteins called histones. Action of methylase enzyme at certain places on histones leads to tightening of chromosomes and silencing of the genes, while actions of a demethylase enzyme can remove the methyl groups on the histones and relax the chromosome for gene expression.

Another important aspect that the study found is the role of a demethylase enzyme namely JMJD3 (Jumonji Domain containing protein) that is responsible for demethylating histones resulting in the expression of the above mentioned genes. JMJD3 is repressed by a complex of proteins and one of them called MINT/spen was not found to be produced in Foamy Macrophages, thus allowing JMJD3 to express the genes involved in Foamy Macrophage development. Also, the gene to produce MINT/spen is inhibited by the action of MUSHASI - an RNA binding protein, which binds mRNA at a specific site. MUSASHI restrains MINT/spen from getting translated and the absence of MINT/spen leaves JMJD3 free to demethylate histones. Thus, the chromosome gets relaxed at the genes required for FM generation and they get expressed. The lipid droplets that provide a survival niche to the bacterium and help evade immune responses are produced. And finally, MUSASHI is NOTCH1 responsive - meaning that it could be expressed by NOTCH -1 signaling, which enables the bacterium to manipulate.

Though it is too early to claim any therapeutic intervention based on epigenetic modifications of the host cells, Ms. Mahadik opines - “Histone marks, DNA methylation, that are marks of epigenetic modification could serve as biomarkers for the disease. These marks are going to remain in the host genome and thus could be used as epigenetic memory in the design of vaccines.”

This research is a key insight that could drive the direction for drug development against TB. “Study of factors leading to reactivation from latent TB into active TB could be vital to completely eradicate the disease. Knowledge of mycobacteria governed epigenomics would also aid the understanding of pathologies associated with the disease progression. Further, mycobacterial infection results in a predisposition to several other infections and it would be fascinating to note the impact of epigenetic factors during co-infections”, signs off Ms. Mahadik stressing the importance of such studies.

Tag: foamymacrophagesMycobacterium Tuberculosissignalling pathwaysMCB
by Dennis CJ January 17, 2017

Photo: Seshadri K S

‘We are all made of stardust’ goes the common saying. The phrase is more than just rhetoric; it alludes to the formation of atoms and molecules in the universe. Most atoms and a few molecules around us were mostly formed in the bowels of exploding stars, which then went on to form planets, oceans, living organisms and everything in between. Now, a collaborative study by Raman Research Institute (RRI), Bangalore, Indian Institute of Science (IISc), Bangalore and P. N. Lebedev Physical Institute, Moscow, is studying the processes that may have led to the formation of these molecules from the debris of the exploding stars. 

Galaxies contain swirling mass of gases that eventually coalesce under gravity to form stars. “In the most common types of galaxies, like our Milky-Way, the star formation rate is between 0.5 and 1 solar masses per year, resulting in one or two supernova explosions in a century”, explains Dr. Arpita Roy, a former research student at RRI and IISc.  Occasionally however, events like close-encounters or collisions with other galaxies can shake things up within a galaxy, causing the rate of star formation to shoot up by 10 or even 100 times. Such galaxies, referred to as starburst galaxies, act as an important window into the birth and evolution of stars and galaxies. “Central regions of starburst galaxies have very high densities and are called starburst nuclei. They are the hubs for very high star formation and hence are, in general, quite violent. They are also the sources of energy, momentum, mass and heavy chemical elements”, adds Dr. Roy.

The current study focused on the processes that lead to the formation of molecules in expanding shock waves caused by supernovae, called superbubbles. “Multiple coherent supernovae in the starburst nuclei create strong shocks or superbubbles. When these strong shocks move through the interstellar medium (ISM), they sweep up ISM materials and store them in dense, thin shells behind the shocks, which further cool and form molecules. These molecular clouds could then again be sites for the formation of second generation of stars”, says Dr. Roy. “It has always been surprising to see how molecules can survive in these extreme violent environments in the central regions of the starburst galaxies. Now, there can be two situations: either these molecules are the old ones, which were originally there in the parent molecular clouds, where the massive stars were initially born, or, these are the new molecules formed in-situ in the dense superbubble shells. Our model tries to understand these issues in detail and describes that molecules in observed outflows in the central regions of the starburst galaxies can be explained by in-situ molecule formation processes" she adds.

The researchers proposed a simplified model in which superbubbles are considered to be roughly spherical in shape. Further, other factors such as the dynamics (velocity), the density and temperature of such a spherical superbubble are calculated. With these values entered in to the model, the researchers ran simulations to predict the processes, which lead to molecule formation. “We performed numerical hydrodynamic simulations with proper numerical descriptions of thermodynamics with all relevant heating (cosmic-ray heating, photo-electric heating, ionising radiation, dust emission etc.) and cooling mechanisms, which then determines the conditions for efficient molecule formation”, explains Prof. Yuri Shchekinov, a Professor at P. N. Lebedev Physical Institute. This model of molecule formation is a collective effort by Prof. Biman Nath at RRI, Prof. Prateek Sharma at IISc along with Dr. Roy and Prof. Yuri Shchekinov

Although a simple model, the simulations matched the observations of molecular outflows in superbubbles with simple spherical morphology. This further confirmed the accuracy of the proposed model and hence the processes which govern molecule formation within a starburst nuclei. The proposed model opens up the prospect of studying other aspects of galaxies and the Universe as a whole. “The detailed information of mass, energy and transport of heavy elements to the interstellar medium (ISM) help us study the overall evolution of the ISM of the host galaxies. These heavy elements may sometimes also enrich the intergalactic medium (IGM) via superbubble evolutions. Therefore, for many astrophysical purposes, such as how stars form and evolve to affect the evolution of the ISM and also the Universe in general, starburst nuclei are the most important experimental sites”, concludes Dr. Roy.

Tag: superbubblemolecular outflowsupernovaeRRgalaxyAstronomy
by Dennis CJ January 14, 2017

Photo: CBR, IISc

The Centre for Brain Research (CBR) at Indian Institute of Science (IISc), Bengaluru, received a generous endowment from former IAS officer Ms. Sharwaree Gokhale who passed away on 15th January 2016. In her will, Ms. Gokhale donated a major portion of her estate to CBR. Her contribution would help progress our understanding of the most complex organ that we know of - the human brain.

Ms. Gokhale joined the Indian Administrative Service (IAS) in 1974, where she went on to work for 36 years under the Maharashtra state cadre. During her time as an IAS officer, she undertook several public service projects, including effectively managing the swine-flu pandemic in Maharashtra. She was also instrumental in implementing the Sarva Shiksha Abhiyan programme under the former Prime Minister Atal Bihari Vajpayee’s government, aimed at universalisation of elementary education in Maharashtra. She was admired by her peers for her incisive analytical ability and principle approach to solving problems. Her passion and dedication was recognized by the state, and in 1979 she became the first woman to become the District Collector in the state of Maharashtra, breaking long held traditions and conventions. Her dedication towards public service and the realization that human progress required investment in scientific research, motivated her to make this donation to CBR.

CBR, an autonomous centre of IISc, was established with the assistance from Pratiksha Trust, a charitable trust set up by Infosys co-founder Kris Gopalakrishnan and his wife Sudha Gopalakrishnan, to assist and advance research in basic and clinical neurosciences. Current research at the centre focuses on preserving cognitive functions during ageing and developing neuromorphic computing and algorithms to better understand the functions of the brain. Although still in its infancy, the centre has embarked on a number of ambitious projects with support from Centre for Neuroscience and other departments (Computer Science and Automation CSA) at IISc. The centre also collaborates with research hospitals across the country, like National Institute of Mental health and Neurosciences (NIMHANS) to better our understanding of ailments affecting the brain and to provide clinical solutions.

As a public servant, Ms. Gokhale indeed dedicated her life to improving the life of others. With her donation, she continues to contribute to the progress of human kind even in her death.  Her gift to CBR will help in furthering our knowledge of human brain especially with reference to age-related brain disorders

Tag: Centre for Brain ReserachCBRendowmentdonationbrainIAS
by Saraswathi January 11, 2017

Ribosomes are molecular machines that make proteins in cells. That the ribosomes are important can be judged by the fact that the cells spend about 40% of their energy in assembling them. In bacteria, ribosomes are made up of a large (50S) and a small (30S) subunits. Flaws in the assembly and maturation (biogenesis) of any of these subunits affect protein synthesis in various ways and often result in the organism’s intolerance to cold, and impact their resistance to drugs and pathogenity. In higher organisms (including humans), defective biogenesis of ribosomes could lead to various diseases. Hence, an understanding of how cells manage accuracy in the complex process of ribosome biogenesis is of utmost importance in developing therapeutic interventions. Now, a study from the laboratory of Prof. Umesh Varshney at the Department of Microbiology and Cell Biology, Indian Institute of Science (IISc), Bangalore, has unravelled the mechanism behind synthesis of ribosomes.

“Ribosomopathies are disorders that occur due to defective ribosome biogenesis/maturation. Our study has discovered a new step in the ribosome maturation pathway. These studies provide us with a good model to understand how the ribosomes that do not mature, affect translation of various mRNAs in the cell”, explains Prof. Varshney, describing the application of this research. Using E. coli, a type of bacteria, the researchers have studied the role of a type of RNA known as initiator transfer RNA (i-tRNA) in the formation of ribosomes and the effects of immature ribosomes on protein synthesis.

Expression of the genetic information in organisms occurs mainly in two stages. In the first stage, called transcription, the information contained in the cell’s DNA is transferred to a “messenger” RNA (mRNA). Protein synthesis actually occurs in the second stage called translation, which is sub-divided into three steps - initiation, elongation, and termination. At the initiation step, the small subunit of the ribosome binds with the i-tRNA and the mRNA at its “start” location, and joins with the large subunit of the ribosome with the help of many small proteins. This collaborative set up of the ribosomal subunits, mRNA and i-tRNA ensures correct encoding of the genetic information in the mRNA into protein. In the elongation step, the ribosome makes the protein by bringing together the building blocks of protein - amino acids- in response to the information available in the mRNA. The termination step is reached when the ribosome encounters the “stop” location on the mRNA, thus bringing the process to a stop. This step is then followed by a process that separates the two subunits of ribosomes so as to make them available for another round of protein synthesis.

In the current investigation, the researchers carried out an indepth study using Northern blotting, a technique used to detect the RNAs of interest from the entire RNA mix, on two strains of E. coli - a wild type strain and a mutant strain with three of its four i-tRNA genes removed. The mutant strain showed sensitivity to cold and the researchers also observed an increased accumulation of immature 16S rRNA which is a sub-component of the 30S (the smaller subunit) ribosome. Further, when the missing i-tRNAs were genetically introduced into the mutant strain, both cold insensitivity and the maturation flaws in 16S rRNA were corrected.

The researchers used specific inhibitors to halt translation in cells at different stages. They found that most of the inhibitors did not significantly impede 16S rRNA maturation; however, the inhibitors that interfered with i-tRNA binding to the 30S ribosome did, highlighting the importance of  i-tRNA dependent ribosome maturation during the pioneering round (the first time a newly assembled 30S ribosome is used) of translation initiation. “Pioneering round of initiation seems to flag the culmination of the ribosome maturation process”, suggests Dr. Varshney.
This study provides a model to study the role of i-tRNA in ribosome biogenesis and also alludes to the translation stage at which maturation occurs. “We will now follow up how deficiency of i-tRNA affects translation of the mRNA pool in the cell. Deficiencies in ribosome maturation would result in the generation of heterogenous pool of ribosomes which could translate the mRNA pools differentially and result in an altered proteome in the cell”, concludes Dr. Varshney, talking about the future course of research.

Tag: MCBMedicalCell Biology
by Bhargavi January 10, 2017

Photo: Siddharth Kankaria

Science has established that the father’s sperm, which fertilizes the mother’s ovum resulting in the formation of an embryo, decides the sex of an individual. So it’s only logical that if the ‘male factor’ of the sperm/ovum relationship is damaged, the product will be too. Now, a recent collaborative study by a team of researchers led by Prof. Hanudatta Atreya of the Indian Institute of Science, Bangalore, and Prof. Satish Kumar Adiga of Kasturba Medical College, Manipal, has found that if the sperm, set to fertilize a particular ovum, has damaged DNA, it affects the metabolism of the embryo that it fathers. The study was conducted using samples of sperm and ova from couples undergoing Intra-Cytoplamic Sperm Injection (ICSI), a popular technique to help infertile couples conceive.

The study focussed on analysing the usage patterns of different amino acids, sugars and other nutrients, also called metabolites, by the embryos formed from damaged sperm cells. These observations performed using Nuclear Magnetic Resonance (NMR) – the same principle behind MRI scanners- were then compared with the metabolites used by embryos formed from healthy sperms. In addition, the study also analysed the differences in the nutrient requirements of embryos fertilized with healthy sperms and those with damaged DNA.  “These non-invasive biomarkers will now identify embryos with high amounts of DNA fragmentation and avoid transferring them to patients as they will eventually fail to implant or result in early pregnancy loss”, says Prof. Adiga explaining the importance of this study on assisted reproductive technologies.

During the study, the researchers subjected the collected sperm samples to a biochemical assay to visualize any defects present in the DNA and the damaged sperms were kept in a culture medium. They observed that the damaged sperms utilized metabolites to different extents than healthy samples. For example, they used more of glutamine, an amino acid, than healthy sperms. The researchers also used biochemical assays to study the differences in embryos conceived from normal and genetically abnormal sperms. The embryos formed from healthy sperms utilized more sugar (pyruvate) and less of the amino acid alanine.

Based on these observations, the researchers hypothesised that the differences in metabolite uptake in embryos from damaged and healthy sperms are probably efforts to correct the sperm mediated DNA damage to the embryo. After all, an embryo is DNA coding derived from its mother and father in equal parts! Ergo, it stands to reason that if 50% of its DNA has flaws, the embryo will do what it can to reverse or correct these flaws.

Though the study successful shows the resulting metabolic differences due to damaged DNA in sperms, it could not find a direct correlation between sperm DNA damage and the composition of the embryo since there is no currently available non-invasive technique to analyse the composition of embryos without damaging it.  Further research in this area could lead to a possible technique to analyse the embryo composition without destroying it.

“This study reinforces our belief that small molecule metabolites are valuable biomarkers of cellular conditions and the power of NMR spectroscopy in unravelling this information in a non-invasive manner,” asserts Prof. Atreya. The next step would be assisting the embryo to correct the DNA damage suffered from the hisperm or to do so in vitro, resulting in healthier embryos. Studies such as these lay foundation to a healthier society around us.

Tag: Division of Clinical EmbryologyNMR Research CentreEmbryology
by Indulekha January 6, 2017

Black coloured rooftops have become the norm of many of the cities’ landscape with increasing number of houses switching over to sustainable, efficient and clean energy source – solar energy. Solar-thermal power systems that convert solar energy to heat or electricity are becoming ubiquitous. These systems typically consist of a flat plate collector that utilizes solar absorber coatings to get maximum conversion efficiency from incident solar radiation to heat. These collectors are coated black to enhance the absorptance- the effectiveness of absorbing radiant energy. Now, a group of researchers, led by Prof. Bikramjit Basu from the Material Research Centre at the Indian Institute of Science, Bangalore, and Dr. Harish C Barshilia from CSIR-National Aerospace Laboratories, has developed a new, colourful coating for flat plate collectors, thereby increasing its absorptance without compromising the aesthetic appearance of the roofs where they are installed.

This research is a part of a gigantic Indo-US solar energy research project called SERIIUS, launched to discover the revolutionary power of solar energy by photovoltaic (PV) and concentrating solar power (CSP) where IISc has tied up with the National Renewable Energy Laboratory (NREL), USA. “As a part of the SERIIUS project, our research group has been actively working on developing solar selective absorber coating for last few years. Prof. Kamanio Chattopadhyay from Materials Engineering and Interdisciplinary Centre for Energy Research, IISc is instrumental in successfully accomplishing this work”, says Atasi Dan, a PhD scholar at Materials Research Centre, IISc and has been working on the project since March, 2014.

“To meet the ever increasing energy demands of mankind, it is necessary to harness the renewable source of solar energy. One of the most efficient ways to harness solar energy to generate solar thermal power is through the photo-thermal route, wherein suitable concentrated collectors are coated with spectrally selective coating with desired properties”, says Dr. Barshilia, explaining the motivation behind the study. An ideal solar absorber needs to absorb much of the incident solar radiation and emit very less thermal infrared radiation. These properties depend largely on the material and the coating of the absorbers. Most of the spectrally selective coloured paints used as absorber coatings have the limitation of high emittance.

The multilayer absorber coating developed by the team is fabricated using tungsten, aluminium, Nitrogen and Oxygen. The team had to address the challenge of ensuring maximum absorptance while minimizing heat loss in the absorber, and also improve the environmental and thermal stability of the coating that can be affected by humidity, short-term thermal shock, etc. This coating exhibited coloured appearance, a long-term thermal stability of up to 500°C in air for 150 hours, and a durability of 25 years. The aluminium oxide layer provided thermal and chemical stability for the coating while tungsten prevented diffusion of iron and chromium atoms from the stainless steel substrate towards the coating.

The researchers have developed an improved solar absorber coating that has four layers - a metallic reflector, an absorber with high metallic content, a semi-transparent layer with low metallic content and an anti-reflection layer. “We have performed more than 100 experiments by varying a number of parameters to achieve desired performance of the multilayer stack. A slight change of these experimental parameters may result in drastic change in the selective performance of the coating”, explains Ms. Dan. “Our aim was also to find out the physics behind achieving such an outstanding selectivity and the colour appearance of the coating”, she adds. “The colour of the coating had to be carefully chosen since it is based on the part of the solar spectrum that is being reflected - attractive colours result in high reflectance and low absorption. We have modulated the number of layers in the coating to get a blue colour”, Prof. Basu said.

Concentrating Solar Power (CSP) systems – the technology that uses mirrors and lenses to concentrate sunlight onto a small area to produce heat and then subsequently electricity - are carbon neutral unlike fossil fuels, have lower operational cost and supply energy during high demands since they store energy. “The newly developed solar selective absorbers will improve the efficiency of these CSP systems. Further research to develop new solar selective functional materials will certainly address the global energy-related challenges”, concludes Prof. Basu, talking about how this innovation may help reduce the dependency on imported oil. 

Tag: solar converterssolar panelscolourroofMRCIIScCSIR-NALSERIIUS
by Mira M January 5, 2017

Photo: Siddharth Kankaria

The Internet is a bottomless mine of information in various forms – text, videos and images. Organizing this information for easy search and retrieval is very beneficial to internet users, and poses challenges to computer scientists. While lot of research progress has been made about categorizing textual data, the same cannot be said about images and videos. A group of researchers at the Indian Institute of Science, Bangalore, has been attempting to make video search on the Internet user-friendly. In a recent paper, Prof. Chiranjib Bhattacharyya and a Ph.D. scholar Dr. Adway Mitra, at the Department of Computer Science and Automation (CSA), and Prof. Soma Biswas from the Department of Electrical Engineering, have presented techniques to this end.

The researchers have developed the idea of providing “video summaries” so that users can search and find interesting videos easily. “If you want some specific information from a set of videos, you do not want to watch all of them to know if they are relevant for you. That's why we need video summaries that can be generated automatically and are informative to users”, says Dr. Mitra on the purpose of this study.

The researchers focused on the objects in a video in order to provide a concise summary using frames from different parts of the video. “By making use of object detectors and action detectors, the computer can know the contents of an image, with limited accuracy.”, explains Dr. Mitra.Finding the objects in a video is based on the technique of ‘entity discovery’ - identifying a particular object or person and tracking all of their occurrences in the video. A ‘tracklet’ latches onto a particular entity and is a collection of frames containing that entity. The process of grouping tracklets based on the entities associated with them is called ‘tracklet clustering’.

Conventional techniques of entity discovery have major drawbacks. They struggle in cases where an entity appears in a video for a while and then reappears at a far later time. Entity detection in frames is based on computer vision that is a relatively new area of research and 100% accurate detection at all times is still a challenge. Also, existing methods fail to work satisfactorily with streamed videos since the algorithm will get only one shot to pass over the entire video sequence.

To address these drawbacks, the researchers propose the concept of ‘temporal coherence’ with two levels - detection and tracklet. At the detection-level, it is assumed that there will be little change in features within a tracklet since the focus is on a single entity. Tracklets that are closer to each other in space and time, but are non-overlapping, are likely to focus on the same entity. But, overlapping tracklets must focus on two separate entities. “Since no meta data is available with the video, it is important to leverage structural properties like temporal coherence”, says Dr. Mitra.

Since the algorithm will not know the number of entities that are in a video until it has ‘watched’ the entire video, it needs to be adaptable to new discoveries made during the video processing. The researchers used a statistical modeling approach called Bayesian nonparametrics that adapts very well to an unknown number of entities.

This method is able to prevent or reduce cases where a tracklet supposed to be tracking person A ends up attaching to person B compared to other methods. It was also found to work well with streaming videos, beating other models. This study is one of the many attempts to make video tagging and video summaries automated. Hopefully, efforts like this may reshape the tedious task of video searching.

Tag: Computer Science and AutomationYou Tube
by Indulekha January 4, 2017

Photo: Gururaja K V

Global Climate Models (GCMs) are mathematical models to understand and predict the Earth’s climate by projecting the real-world processes over time. These simulation tools help to predict future climate variables that will be useful to develop sustainable long, medium and short-term water resource planning strategies. A new study by a team of scientists - Prof. D. Nagesh Kumar from the Indian Institute of Science, Bangalore and Prof. K. Srinivasa Raju from BITS-Pilani, Hyderabad campus, has analyzed numerous available GCMs to choose the best that would be applicable in the Indian context. Such analysis helps in developing the best resource planning strategies and the best climate models that can be used for localized needs.

Clustering is a method of grouping a set of objects or data points according to similarity, and then extracting information from this data set to a logical structure. The researchers employed various statistical tools to group 36 GCMs from Coupled Model Intercomparison Project Phase 5 (CMIP5) database with reference to maximum temperature (MAXT), minimum temperature (MINT) and the combination of maximum and minimum temperature (COMBT) in India. CMIP5 aims to provide a framework for how to conduct coordinated climate change experiments during the next five years. Assessment of these temperature related variables is essential because they are instrumental in managing the hydrological cycle.

Clustering of GCMs is important because most of them use similar numerical schemes, parameterizations, or are developed by the same agency. “Cluster analysis helped to suggest representative GCM instead of a number of GCMs which are similar,” explains Prof. Raju. Clustering of data is done by K-Means clustering followed by obtaining the optimal clusters of GCMs wherein the GCMs are optimally divided between the clusters. K-means clustering is a statistical method to partition ‘n’ number of observations into ‘k’ number of clusters based on attributes of the observation. Each observation is allotted to a cluster that has a mean value closer to the observation.

The researchers then applied cluster validation methods like Davies–Bouldin Index (DBI) and F-statistic to measure the quality of the chosen group and determine the optimal number of clusters of GCMs. They observed that most of the GCMs are similar and found that the optimum cluster was 3 for MAXT and 2 each for MINT and COMBT. Based on these, an ensemble of GCMs was suggested.

In India, climate studies based on temperature are lesser than studies that rely on precipitation patterns. This study is the first to employ K-Means cluster analysis for choosing an ensemble of Global Climate Models for Indian climate. “The present methodology, in our opinion is the first of its kind where global climate models were clustered seamlessly using twin modeling structures: First modeling structure is based on K-Means cluster analysis to cluster the GCMs whereas second modeling structure is related to Cluster validation techniques such as Davies- Bouldin index and F-Statistic to determine optimal clusters of GCMs,” says Prof. Nagesh Kumar. The ease with which the methodology can be applied and replicated makes this important study a pivot for future endeavors on climate impact assessment studies.

Water scarcity in various parts of the country, especially for clean, drinking water, confirms the need for efficient hydrological modeling applications like rainfall-runoff modeling studies. The inferences drawn from this study will make a remarkable turnover in the current water conservation strategies. “The ensemble of Global Climate Models chosen for different situations can help in efficient reservoir design, drinking water requirements, etc. which helps the public as a whole”, concludes Prof. Nagesh Kumar.

Tag: Centre for Earth Sciencesclimate changeModellingWater management
by Siddharth Kankaria January 2, 2017

Photo: Siddharth Kankaria

Not many young professors are as driven as Professor Prabeer Barpanda who has been donned with an unbelievable streak of academic awards. A professor at the Materials Research Centre, Indian Institute of Science, Bangalore, Prof. Barpanda is the winner of the Indian National Science Academy Young Scientist Award, 2016. He became the first Indian to receive the Energy Technology Division Supramaniam Srinivasan Young Investigator Award – an annual award given by the Electrochemical Society (ECS), USA, for 2016. In addition, he is also the first Indian to receive the American Ceramics Society’s Ross Coffin Purdy Award, 2016 awarded in October.

Prof. Barpanda’s research is focussed on developing new materials for lithium and sodium ion batteries. He is using the energy-savvy “sonochemical synthesis” and has synthesized a series of electrode materials. The electrode materials developed in his lab with the application of this technology posses very high conductivity and are highly electro-active. In the last two years, Prof. Barpanda’s lab has successfully made two new materials using low-temperature methods – one manganese-based and the other cobalt-based. The research group has also reported the crystal structures of these new materials to ICSD, the world's largest database for inorganic crystal structures.

“In every battery, we have a battery material called cathode which contributes directly to the overall energy density – how long the battery will last or how many hours will it go on for. So, if we want to make longer lasting batteries or safer batteries, then it is important to have newer battery materials”, explains Prof. Barpanda. “At higher voltages, the energy density of the battery should increase easily, depending on the local crystal structure of iron, Cobalt, or Oxygen. Thus, we want to deliver a new inorganic material which can operate at a higher voltage”, he adds explaining the motivation behind his lab trying to make battery materials that operate at high voltages.

Prof. Barpanda has visited more than 40 countries during the course of his academic career and education and has the distinction of having academic degrees from three continents. After his Ph.D. from Rutgers University, USA he pursued his post-doctoral studies in universities in France and Japan before joining IISc. He enjoys travelling and experiencing different scientific cultures and personally considers US, Europe and Japan as the three scientific pillars in his field of research.

In the near future, Prof. Barpanda hopes to have a fully equipped lab at IISc with all necessary, state-of-the-art equipments in order to take his research to the next level. He aims to bring out a new battery material that has been researched and developed entirely in India. Besides his research goals, he also aspires to be invited as a speaker in some of the world’s top research meetings in his field. He enjoys his role as a teacher and wishes to be a learner in life. “My post-doc advisor once told me that we are all students of different age – so I’m not a faculty here, but just another good student here”, he signs off.

Tag: electrodesbatteriesMaterials Research CentreIISc
by Siddharth Kankaria December 29, 2016

Photo: Siddharth Kankaria

Chandan Saha of the Computer Science and Automation department, Indian Institute of Science (IISc), Bengaluru is the winner of two prestigious national awards – the Indian National Science Academy (INSA) Young Scientist Award, 2016, and the Indian National Academy of Engineering (INAE) Young Engineer Award, 2016. He works in the areas of complexity theory and algorithms, and his lab is currently trying to study arithmetic circuits to understand computational efficiency as a function of time and computational memory.

 “Circuits generally come in two flavours - arithmetic circuits that are used for studying arithmetic operations, and Boolean circuits that are more fundamental and closer to the gut of computation,” explains Saha. In his view, circuits are just one of the formal mathematical models that can capture the essence of computation. Saha’s lab is studying arithmetic circuits that can be used to analyse problems in linear algebra, like determinant and matrix product computations, solve polynomial equations used in robotic arm movements, in information and coding theory, as well as in cryptography. The lab has a Ph.D. scholar and three Master’s students actively involved in its work.

Saha is an alumnus of Jadavpur University, Kolkata and credits his success to the influence his teachers had on him. His Ph.D. advisor at the Indian Institute of Technology, Kanpur, Prof. Mahindra Agarwal’s working style has been a great source of inspiration to him. “I only realised it in retrospect how important it is for a Ph.D. student to grow independently and develop his own thought process and his own chain of ideas,” he recalls while fondly recollecting his college days.

Being an academician, Saha sees the need to attract more students towards academia. Being inquisitive, patient and perseverant are some of the characteristics he desires to see in his students rather than just being able to score well in exams. This, he says builds the ability to catch up to the research dimension, which requires long hours of thought process. In his opinion, a challenge for our schools and undergraduate institutions is to appreciate and encourage creativity in each student instead of putting too much emphasis on grades and rankings.

Saha has been at IISc for the last four years and has seen his area of research scale new heights. “Arithmetic circuit complexity is a relatively new terrain in mathematics and a fertile area. I plan to stay here and generate new ideas as long as there is momentum and progress. I also want to train Ph.D. students and focus on teaching”, he signs off with a smile.

Tag: CSA
by Siddharth Kankaria December 28, 2016

Photo: Siddharth Kankaria

Dropped your mobile phone? You may soon stop worrying about it, thanks to the newly discovered phenomena related to carbon nanotube foam used as a shock-absorbent material in mobile phones. As a material scientist, Prof. Praveen Kumar’s work on studying the mechanical behaviour of materials has earned him various awards, the most recent ones being the Indian National Science Academy Young Scientist Award, 2016, National Academy of Science, India -Young Scientist Platinum Jubilee awards - 2016 and Associate of Indian Academy of Science. In his Thermo-Electro-Mechanical Behaviour Lab at the Department of Materials Engineering, Indian Institute of Science, Prof. Kumar and his students study the effects of size and electric fields on mechanical properties of materials and materials processing.

The effects of electric field on mechanical properties of materials are of paramount importance at really small scales, when they are used in chips and micro-electronic apparatus found in devices like mobile phones and laptops. As devices become thinner with less airspace, they need to be shockproof, too. Prof. Kumar’s lab has experimented with carbon nanotubes to devise such a shockproof material. “The carbon nanotube cellular network that we have developed looks like a black foam which is approximately a millimetre thick. If you zoom into it, you can see it is made up of bundles of carbon nanotubes (CNTs) and there are a lot of open spaces between the CNTs, and each CNT is a multi-walled structure”, explains Prof. Kumar.

During their research, Prof. Kumar’s team found that when an electric field was applied on the new foam material, it developed a strain, which led to the foam lengthening in size. Further studies examined how fast could this material responded to stimulus and was able to absorb a shock. “These CNT foams can be used as a replacement for shock absorbent layers in devices like cell phones. They can also be used in any application that requires energy absorption. In short, these CNT foams have very good shock absorption properties, which can be improved substantially by applying an electric field across them”, says Prof. Kumar on the potential applications of these CNT foams.

Being a strong advocate of inter-disciplinary research, Prof. Kumar feels that problems of the future will need multiple perspectives to be solved, which comes from such research. Collaboration, he opines is the best way to build a team of people with different skill-sets to solve a problem. “Many a times after finishing your Ph.D., you don’t know everything! When you encounter a new problem, it will not necessarily segregate itself into a biological or a mathematical problem - Nature doesn’t know what is physics or chemistry or biology, or even what science is and what isn’t! It is we who have defined these categories”, he asserts.

Prof. Kumar attributes the success of his life and his lab to multiple players – his family, his students, and the institute. “The most important thing in IISc is that its atmosphere allows you to do whatever you want to do. And in some sense, in very subtle way, it also wants you to excel in whatever you are doing! The environment that IISc has doesn’t let you slow down”, he quips. “Who you are, is not who you are, on your own. It’s a process or a journey, where you find people – who can be anywhere – that influence you”, adds Prof. Kumar recalling those who have shaped his journey so far, as he signs off.

Tag: Department of Materials Engineering
by Ramya December 27, 2016

Photo: Dennis C J

The world is definitely getting hotter, thanks to climate change – the topic that is hottest at the moment! What responsibilities do scientific institutes and businesses have, to make this world a cooler place, quite literally? Who can explain this better than Ms. Gilbert, Head of Policy at the Grantham Institute - Climate Change and Environment at Imperial College London! Ms. Gilbert is engaged in connecting relevant research across universities with policy-makers and businesses. In a candid interview during her visit to the Divecha Centre for Climate Change at the Indian Institute of Science, she opens up on her role and its challenges, the opportunities this situation presents, and her opinions on actions that need to be taken in tackling climate change.

“The scientific community has a huge, untapped potential as a vast store of information that can be useful to society”, comments Ms. Gilbert opening up the discussion. “On the other side, you have a group which is struggling to find ways to solve economic, environmental and social problems at a practical level. Someone has to make this a two-way connection; someone has to build this bridge”, she expresses, explaining why her role is critical in today’s scenario. At present, businesses, media and academia speak different languages; each bringing with them their own form of exclusivity. It is a huge challenge to have these groups understand each other and see eye to eye. Hence, the role of translators who can build this bridge between these different groups becomes extremely important.

Talking about the challenges translators like her face, Ms. Gilbert exclaims – "It was a big culture shock for me!” Being new to this field, she had to immerse herself in academia, build trust with a lot of researchers, get to know how they work and learn their language. She recollects her strategy of talking to people who had spoken about their research in public in the past and were willing to talk to her, and then talking to newer people who would be far less comfortable simplifying their research and who would have reservations about it. “But at the end of it all, I find it deeply satisfying that I am able to get this kind of work done”, she says with a smile.

Ms. Gilbert’s work plays a critical role in helping policy makers make the right decision. Often, it is believed that all the information that policy makers need is readily available in the public domain. However, in reality, it is an enormous task for policy makers to access, sort and prioritise the information they need. And how does policy making work? “It starts with some clear top-down political priorities informed by public opinion and pressure, followed by instructions to civil servants to make a suitable policy for implementation”, explains Ms. Gilbert. This process, she says, includes research and consultations with stakeholders like local people, NGOs such as environmental pressure groups and trade unions and companies, which results in a draft. Depending on the legislative status of the draft policy, this draft could result in standards, legislation that requires a Parliamentary process, or the creation of voluntary or other mechanisms. And who makes the decisions behind these policies? “Generally, policy makers can range from elected representatives in the parliament to civil servants operating in their office”, she adds.

In today’s world, it is increasingly challenging for policies to strike a balance between climate action and economic development in developing countries like India. Policy makers decide what form a certain law will take, which is extremely important for climate positive action at the grassroots. “Tension between economic growth and environmental change is a key challenge. Since developing countries are also home to the populations worst affected by climate change, they have serious challenges in terms of successful adaptation and mitigation strategies. The need of the hour is to arrive at creative solutions - a win-win policy for both parties”, opines Ms. Gilbert. “Some countries suffer due to absence of capacity to make important policies. Fortunately, India is not among those since it has a good research network built around addressing these issues”, she says. Nevertheless, there is hope for developing nations. “They have a wonderful opportunity to chart a new course of climate compatible economic development. They have the example of the developed countries and they should know what consequences await those trajectories. Don’t repeat what we’ve done. It doesn’t work”, she warns.

Another concern that Ms. Gilbert points out in tackling climate change is the fact that people all over the world have always been reactive, rather than proactive. “Attribution of extreme events is really important to make people take climate change more seriously, especially in the light of the recent El Niño event. If we could tell people how much of recent extreme droughts and storms are due to human influence on our climate, we would be able to stimulate more action. I believe that we should offer realistic and pragmatic solutions to people in order to combat climate change”, she articulates.

Talking about reasons for the reactive response, Ms. Gilbert points out an interesting tendency among scientists to be over cautious when making predictions in the face of uncertainty. There is consensus among activists and policymakers that there are enough studies on the causes, effects and factors that drive climate change. “What the world needs now is action! Infrastructure, investment in climate change mitigation measures and sustainability should be our focus. Infrastructure such as water, transport and grids need to be made more sustainable. Engineering solutions such as carbon capture and storage solutions for power need to be tested immediately and adopted”, she urges.

When asked if concepts such as anti-consumerism, de-growth and reduction of resources help in tackling this situation, Ms. Gilbert is quick to point out its drawbacks. “I think it is not realistic. The juggernaut of economic growth is too big for states to avoid it. For example, India is rapidly developing. You can’t really go and tell people to not want growth, which has brought along a lot of good things. I think the right way to go forward is to harness the power of consumerism into doing something better rather than the other way around.We need to have responsible consumerism and responsible production, now”, she explains.

What can policymakers in India learn from the UK? “The nature of challenges looks different in the two places. But, from my experiences in policymaking in different countries, I see that the crux of the problems in most countries is very similar. I’d be excited about having someone like me at the Divecha Centre for Climate Change here at IISc! Then we’d be able to probably draw on these similarities and work together to solve those issues”, she signs off.

Tag: Divecha Centre for Climate Changeclimate changeInterview
by Dennis CJ December 15, 2016

Photo: Mayank Shrivastava, DESE

In a major breakthrough in the field of graphene based electronics, researchers from the Indian Institute of Science, Bangalore, have shown a big jump in understanding the quantum nature of graphene’s interface with outside world. The research team lead by Prof. Mayank Shrivastava (Department of Electronic Systems Engineering), studied how the overlap of atomic orbitals between Carbon and metal atoms affects the graphene-metal interface. The study has enabled them to invent novel techniques to engineer graphene contact that has the lowest recorded resistance to the external world. Their discovery and subsequent invention, while breaking several records – including the one from IBM’s research centre in T. J. Watson, USA – has eventually allowed achieving the highest transistor performance. This work, which is co-authored by PhD student Adil Meersha and co-investigators Prof. Srinivasan Raghavan and Prof. Navakanta Bhat is showcased at International Electron Device Meeting (IEDM), the world’s most competitive platform in the field of electron devices, which mostly showcases technology and fundamental breakthroughs in the field.

Ever since its discovery in 2004, graphene – a two dimensional, single atom thick layer of Carbon atoms, has gained prominence in the semiconductor and electronics industry due to its exceptional properties. But, a phenomenon called contact resistance, the resistance offered at the point of contact between the metal and graphene, poses a challenge. “The problem of the contact resistance is, even today, considered as one of the most fundamental bottle-neck in realizing this technology. Until we are able to interface graphene with the outside world with very little resistance, we will not be able to squeeze out its projected performance”, says Prof. Shrivastava on the need to solve this bottle-neck.

Scientists all over the world had believed that the lowest limit on contact resistance was already achieved and not much can be achieved further. This research has now debunked the belief by exploring the theoretical aspects at a much deeper level involving quantum chemistry. In a previous study, Prof. Shrivastava’s team had established a link between unfilled electron orbitals around the carbon nucleus, its hybridization or atomic overlap with metal atom and resultant electron transport from metal to graphene. “Atoms are made of a nucleus surrounded by electrons arranged in several orbits called 1s, 2s, 2p, 3s, 3p, 3d and so on, which have unique shapes depicting the region in which probability of finding the electron is maximum. Each orbit can accommodate a fixed number of electrons and when they are in the vicinity of orbits of another atom, they tend to reshape by sharing electrons – called hybridization, which we engineered and formed bonding channels” – explains Prof. Shrivastava.

In the case of graphene, shared electrons of the neighbouring Carbon atoms fill up the unfilled electron orbits through the process called hybridization. By knocking off some of the shared electrons, the unfilled p orbitals can be filled by electrons in a metal with similar unfilled s and p orbitals. “We were trying to see if defects in graphene could affect contact resistance, from a theoretical aspect. We found that by knocking off electrons from some Carbon atoms, an unfilled “p” orbit becomes available, which allows for a better bonding with the metal through bonding channels. These channels, in turn, reduce the contact resistance”, explains Prof. Shrivastava. The researchers found that focussing a beam of electrons on graphene or bombarding it with Argon or Oxygen ions forms the required defects. This would enable hybridizing metal atoms with graphene.

This discovery could herald a new era in utilizing the underutilized terahertz frequency range, band within the electromagnetic spectrum, lying between microwave and infrared. Due to its safe, non-destructive and non-invasive properties, the terahertz frequency could be used for applications as wide ranging as high altitude communication and faster wireless communication to surveillance and security. “Graphene transistors are expected to be the enabler of THz technology– a billion dollar high end application market, which is still untouched due to unavailability of electronics to control and manipulate THz radiation. With this breakthrough, we foresee commercialization of THz graphene technology in the near future, which was earlier projected to be around 2022”, remarks Prof. Shrivastava.

This study also reflects how exploring theoretical and fundamental concepts of a problem, which many consider an impasse, could lead to technological innovation. The researchers successfully predicted the actual cause behind contact resistance offered by graphene and proceeded to solve it at an atomic level. The process leading up to the design could also set a precedent, where experimentalists opt for a theoretical basis to solve a problem, rather than the usual trial and error method.

    Tag: Department of Electronic Systems Engineering
by Arati Halbe December 13, 2016

Photo: Siddharth Kankaria

Product designers have the responsibility of ensuring the product they design goes to production without any issues. There are various snippets of “knowledge” available in the form of historic production documents, shop floor records, case studies, etc., both offline and online, that can greatly help get an early insight into potential issues. However, a major drawback is the lack of identifying “knowledge” based on this due to their fragmented distribution. Now, researchers at the Indian Institute of Science, Bangalore, Mr. N. Madhusudanan, Prof. Amaresh Chakrabarti and Prof. B. Gurumoorthy, at the Centre for Product Design and Manufacturinghave developed a method for automatically recovering relevant information from document collections. They validated this methodology in the context of aircraft assembly.

Knowledge about problems in assembly or manufacturingthat is generated at different stages of a product lifecycle, can be used in the design or planning phase for other products. These documents help to foresee potential issues in later stages of product lifecycle and seek possible solutions. However, extracting relevant information from these documents can be extremely tedious and time-consuming as most are structured as case studies, and not as knowledge bases. Also, not all information in a given document may be relevant to the topic of interest.

Previous methods that help designers sort documents typically do not “understand” the text, or require large amounts of earlier data or their prior labelling to be available, which is often not the case. “These assume that the documents are tagged with keywords at the time of writing. Unfortunately, such kind of tagged collection is not available for specific scenarios like aircraft assembly”, says Mr. Madhusudanan. The solution proposed by researchers at IISc has a methodology that is based on “understanding” the document contents, rather than just parsing the text. This enables automatic extraction of sections in the document that contain relevant parts.

The proposed solution works on a collection of well-written, rigorously reviewed documents that represent the collective knowledge of a number of experts. Most of these documents are treated as one-way communication, or discourse, from the author to the reader, following a hierarchical, organised structure. There are two steps in the solution; segregation and classification. Segregation is identifying chunks of text that talk about the same topic. Closely related collections of sentences are called coherent chunks. The method scans these sentences and forms a list of entities discussed in them. A lexical database for English, called WordNet, was used here. In the next step of classification, the list of entities is checked to see if they are related to the domain of interest. The chunk is classified as “related” if the similarity of entities in the chunk and the domain of interest are above a certain threshold; else it is “unrelated”. The basis for the similarity are one or more domain ontologies.

A major challenge during the segregation process is the use of pronouns that are frequently used to avoid repetitions. The researchers used existing software that reads through the text, identifies the word to which the pronoun refers to, and replaces it with the actual word. This is called anaphora resolution. It then analyses whether adjacent sentences form a chunk based on the words they contain. If the words are closely related, sentences belong to same chunk. The researchers compared the results of this automated segregation with that of manual segregation and found that the automated segregation had an accuracy of 75%. The validation of the automated classification against manual classification was found to be 85%.

Two key challenges affect the accuracy of the solution - lack of domain specific words in the general English lexicons and the ambiguity caused by using the same words in different contexts. Using further methods for disambiguation, and greater availability of domain specific resources might help mitigate them. This research is pioneering in improvising the design process. “The use of expert knowledge from one phase of a product's lifecycle in another phase is expected to prevent/reduce the occurrence of the same problems. Hopefully this will make assembly less difficult, less dangerous, and more efficient”, concludes Mr. Madhusudanan.

Tag: DesignCPDM
by Dennis CJ December 12, 2016 Photo Credit: Dennis C. Joy   Indian Institute of Science (IISc.) entered a memorandum of understanding (MoU) with Volvo group in India to pursue collaborative research in the field of transportation and automobiles. As per the MoU, Volvo Group Trucks Technology (GTT), the global research, engineering and development arm of Volvo, along with IISc, will embark on research and development in future automotive technologies. The MoU was signed by Dr. K. Paneer Selvam, Joint Registrar of IISc and Dr. Jan-Ove Östensen, VP Advanced Technology & Research, Volvo Group.      IISc stands at the helm of research in the country and has pushed to bridge the gap between research and industrial applications. Through a number of collaboration with industry and other academia, the Institute has been pursuing research that has been consistently creating social impact and improves our day to day lives. “IISc is the leading academic institution which does pioneering research in critical technologies relevant to the automotive sector with an ultimate aim to benefit society. VOLVO has immense knowledge in understanding of next generation requirements to build a sustainable environment for societal benefit. The complementary nature of both institutions present a perfect opportunity to work together to create path-breaking frugal solutions for India, Asia and take them globally” remarks Prof. KVS Hari, Professor and Chairman of the Department of Electrical Communications Engineering.   The Volvo Group is one of the world’s leading manufacturers of trucks, buses, construction equipment and marine and industrial engines. With over 100,000 employees, the group run production facilities in 18 countries and sells its products in more than 190 markets. The Volvo Group is a publicly-held company headquartered in Göteborg, Sweden. The group also collaborates globally with institutes including, Penn State University in the US; INSA in France; and Chalmers University of Technology; Mälardalen University and the University of Skövde in Sweden.    “At the Volvo Group our success is largely due to our ability to continuously develop new innovative solutions that assist customers in their operations and that increase safety and reduce the environmental impact” remarks Mr. Kamal Bali.   The MoU will be for a period of 5 years and would see the collaboration looking in to a wide range of automotive technologies. The research will primarily focus on trucks which could further extend to buses, construction equipment and marine applications. “Transportation is the next transformational area, which will impact society globally.  IISc and VOLVO have a lot of interest in this area where research, innovation and building technologies for the automotive sector is most important” says Prof. Hari.   With expectations of autonomous vehicles and smart cities running high, collaborations between academia and industry has become an important partnership. “Our transport solution products are amongst the best in the world. This means engineers and technologists are our focal point in order to understand vehicle systems, design, testing and develop the next generation of products and services for the transport and infrastructure industries. Such collaboration with academia is important for Volvo Groups strategic long-term initiative to support the delivery of the Group’s Vision. The intention of collaboration is connecting Volvo Group expertise with global academic research and innovation environments in critical technology areas” concludes Dr. Jan-Ove Östensen.”     The MoU leverages the vast experience of Volvo in the transportation sector, with the immense knowledge generation of IISc, to contribute to the society at large. “This MoU is a significant event to foster strong linkage between VOLVO and IISc which is mutually beneficial with an aim to transform the landscape of transportation for societal benefit” concludes Prof. Hari.       Tag: VolvoIISc