On 28th October 2017, a group of panelists in the faculty hall at Indian Institute of Science (IISc), discussed the framework of policies that can help academic institutions embrace open access in letter, spirit and action. The discussion was a part of week-long activities organised by DST-Centre for Policy Research (DST-CPR) at IISc to increase awareness and acceptability for open access publishing in India.

The panel included Jayant Modak, Deputy Director, IISc, Satyajit Mayor, Director of National Centre for Biological Sciences and inStem, Padmini Ray Murray, Vice-Chair, Global Outlook: Digital Humanities, NV Sathyanarayana, Chairman &Managing Director, Informatics India Ltd. and Madan Muthu, visiting faculty at DST-CPR at IISc. The discussion was anchored and moderated by Sunil Abraham, Executive Director, Centre for Internet and Society.

Open access is a form of publishing that makes the fruits of research, such as, journal papers and other forms of data accessible to anyone interested in it, without a cost. World over, a large number of universities and institutions are beginning to give up the library subscription model of publishing to make way for open access, owing to the latter’s lower cost and higher visibility.

In India too, funding agencies like DBT and DST have laid out guidelines that require researchers, to submit their research output in open access repositories. Ironically though, most researchers have shied away from submitting their work in the repositories. Which raises the question, why?

In fact, this was one the first questions that the panelists debated upon. Abraham initiated the discussion by asking the panelists– What are the weaknesses of DBT-DST policy on open access? Why have a large number of scientists not followed the guidelines laid by the policy? Is it because the policy document does not talk about any punitive measures for scientists in the event of not depositing their work in the Institutional repositories(IRs)? And, how can the policy be improved?

Jayant Modak opened the argument by saying that we as a nation are good at making provisions but bad with implementation.He agreed that scientists are yet to warm up to the idea of open access but was disinclined on using punitive measures to force scientists into submitting their work in IRs. Mayor, in agreement with Modak, said that the policy document is advisory in nature and sort of lacks ‘teeth’. However, he too was against the use of punitive measures.

Ray Murray, the third academician on the panel said, that, though the policy talks about staying away from publisher-based metrics like impact factor to assess a scientist's work, it does not provide any information about what alternative metrics can be used to measure it. She suggested that the accessibility of a scientist’s work and how much effort she has put in to make it easily available to non-scientists could be used as a metrics for measurement. She also drew attention to the fact that the policy completely bypasses the requirements of independent scholars and those working in languages other than English. “Which institutional repository should they deposit their work in?”

Sathyanarayana, the fourth panelist and a strong advocate of open access said, the policy document “lacks an aggressive strategy” to drive a disruptive and “fundamentally voluntary model” of adopting open access. He asked the other panelists and the audience, “why have repositories like ResearchGate become so successful and attractive for researchers? Why can’t open access IRs be modelled along the lines of such repositories? His argument was that the IRs can be fashioned in a way to make them a ‘convenient step in the process of research”. One suggestion that he offered was that IRs can be structured as a paper submission platform. So that, anybody who is interested in publishing their work, first puts it up in the IR and only after that the process of going to a journal begins.

Madan Muthu, the fourth panelist and a long-time crusader for open access in India said that scientists in India have stayed away from the open access publishing because they don’t fully realise that in traditional models of publishing, you surrender all copyrights of your work to the publisher. He added that more scientists can be encouraged to adopt the open access model of publishing by making IRs Institute-managed, easier to use and as a mandatory step in the process of publishing.

Mayor added to this argument by saying that the idea of submitting (unpublished) work in an IR is quite similar to the concept of pre-print archives which are fast becoming a powerful way of sharing work. Almost all top journals accept work that has been published in a pre-print archive. In fact, in the physical sciences, people have been using pre-print archives for a long time and now slowly, even the biology community is warming up to it.

Ray Murray emphasised on the need to talk to students about open access and making them aware of the ways to design their metadata so that it is amenable to open access repositories.

As the discussion inched closer to its final moments, it veered off towards the costs of open access publishing. Modak said, that in the last year alone the amount of money IISc has spent for publishing papers has doubled. If all researchers start opting for open access (OA) journals/hybrid-OA journals, that charge the authors nearly double of what traditional journals do, then publishing papers will become unsustainable.

To this, Sathyanarayana said, it may appear that the cost of publishing in OA journals is high, but on a macro level, when you consider the cost of publishing and accessing all the papers published in a year, then the OA model costs much lesser. He added that scientific publishing is the only business in the world where authors (creators of proprietary material) give away all their rights to publishers.”

Backing up the points made by Sathyanarayana, Ray Murray said that in traditional models of publishing the publishers make close to 400% profits. We need to think about, “how much labour we as academics put in for publishers’ profits?”

It is authors’ inertia that is stopping open access from becoming the obvious model of publishing, said, Muthu.

In conclusion, Abraham summed up the arguments and acknowledged that there are many dimensions to open access and an institutional policy on OA cannot be framed in a vacuum. Common people need to participate in the debate to shape the direction the policy takes.

Apart from the panel discussion a poster competition and a quiz competition were organised as part of the OA-week activities. DST-CPR was joined by the student's council at IISc, Centre for Contemporary Studies, JRD Tata Library and IndiaBioscience in organising the activities.

A recent study on oral microbes has found immense richness of bacteria in the saliva of Indians. Some of these bacteria were common to many samples cutting across geographical locations and ethnicities in India. This study by scientists from Centre for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad, and Max Planck Institute for Evolutionary Anthropology, Germany was published in PLoS One.

“Human saliva presents an easy source of studying oral microbiome because of its simple and non-invasive collection method. The microbiome co-evolves with humans and therefore, they are considered as ‘proxy markers’ to study human ancestry and migration”, says Madhusudan R. Nandineni, head of the study team and staff scientist at CDFD.

“The fact that Indian population groups are genetically and environmentally quite heterogeneous is well-recognised, both factors being pivotal in shaping the human microbiome. The oral microbiome is yet largely unexplored in the pan-Indian context,” says Aneesha Acharya, a periodontist at DY Patil Dental College, Pune, and an oral microbiome expert.

The research team analysed salivary samples from 92 volunteers from eight different sampling locations across India. They studied and compared the 16S rRNA region of the genome in all the bacterial samples collected from the saliva. The genome sequence coding for 16S rRNA is highly conserved between different species of bacteria, and hence is routinely used by scientists to establish relationships between different species of bacteria.

Across the three regions sampled—North (Jammu & Kashmir and Uttarakhand), East (Jharkhand, West Bengal, and Assam) and the South (Andhra Pradesh, Telangana, and Tamil Nadu), the researchers found 785 Operational Taxonomic Units (OTUs) and 165 bacterial genera, indicating high level of genetic diversity, almost at par with those seen in African populations earlier.

Samples from West Bengal contained the highest number of unique genera, while those from Tamil Nadu showed the least. Streptococcus spp. was seen to be the major bacterial genus in the samples, followed by genera like Prevotella, Fusobacterium, and Veillonella.

With respect to the shared bacterial genera, there was a significant correlation among the states of the north. However, no correlation was seen among the samples from Assam with those from the other eastern states. Similarly, samples from Tamil Nadu did not show correlation with the rest of the southern states. One interesting observation was that the samples from north India showed only a subtle correlation with those of south India.

660 OTUs were found to be shared among the three regions, out of which 37 OTUs (corresponding to 12 bacterial genera) were found in all the samples, hence constituting the core microbiome for Indian populations. Nine bacterial genera, previously not listed in the Human Oral Microbiome Database (HOMD) were observed. Solobacterium spp., Lachnoanaerobaculum spp., and Alloprevotella spp. were the bacterial species found to be unique to Indian populations.

The new bacterial species observed in this study highlights the importance of studying micro biomes of under-studied populations such as Indians. “When compared to the gut, the oral microbiome is not documented as well and there is much need for further work. While the present study analysed the microbiome at genus and OTU levels, algorithms dedicated to species level resolution of oral microbiota could further our understanding of microbial diversity,” says Acharya.

“One of the main purposes of microbiome studies is to understand how perturbations in the microbiome composition might lead to onset of a disease in humans. Hence, it is first important to know what constitutes the healthy microbiome,” says Nandineni. Going forward, he would like to study the variation of salivary microbiome with time, lifestyle, and food habits of a population.

Dyes are used for producing a variety of colours in the textile industry. But most of these are toxic and difficult to get rid of. Existing methods of water treatment have been unproductive in checking dye contamination. Now, a team of scientists from Shivaji University, Kolhapur have proposed using floating plant beds to remove dyes from industrial discharge. Their study was published in Environmental Research earlier this month.

Several studies (such as here and here) in the past have recommended using plants for bioremediation of wastewater. However, none have made their way out of the labs

One reason for this could be the obvious design flaw, explains Sanjay P. Govindwar the lead investigator of this study. “Plants need soil for growth. But a handful of rooted plants grown at the edge of wetlands cannot neutralise huge quantities of waste water. It is not practical”.

This has been a gaping hole in the research all along.

To plug this gap, Govindwar and his team tried a different approach. They reasoned that for a viable model, plants should have greater access to the industrial discharge. This sparked the idea of a floating plant bed that could be lodged into a treatment chamber. But the success of their design rested on finding plants that could satisfy 3 conditions- decompose the dye, were resilient to the dye and could grow on water beds.

In search of a candidate that would fulfil all the criteria, scientists ventured into a dye polluted site at Maharashtra Industrial Development Corporation, Kagal, India. From this area they selected two plants- Fimbristylis dichotoma and Ammannia baccifera- both of which are annual herbs well adjusted to dyes and grow in a marshy environment.

Next, they tested the plants for their decolourisation potential. Individual plants of F.dichotoma,A. baccifera, and their combination were placed in beakers filled with a commonly used dye- methylene orange. After four days, scientists found huge reductions in the amount of dye left behind in each beaker.

This colour disappearing act takes place in the roots. Once the dyes are absorbed, enzymes in roots degrade these chemicals. Bacteria living in the roots also add to this step by releasing a cocktail of enzymes. F.dichotoma and A. baccifera consortia harbour 5-7 folds greater bacteria than the plants alone. Together the combination group supports 170 unique types of bacteria and therefore shows greater dexterity in degrading dyes.

To prove that decolourised water is indeed safe, scientists analysed the toxicity of cleaved fragments on a common freshwater bivalve. The test confirmed that decolourised dye solution was less toxic.

After passing these benchmarks, the plants were sowed onto an elaborate rectangular floating structure created with dappled PVC pipes. “Each hole was fitted with plastic fillers holding the plant and the soil,” says Govindwar. Nine days after the plant beds were introduced in effluent chambers, the treated textile effluents were assessed for water purity.

F.dichotoma and A. baccifera consortia could remove about 79% of colour from textile wastewater while reducing 66% of the total dissolved solids. The oxygen level in the wastewater also increased and the pH was reverted to normal values.

“A strong point of this method is that it can be applied for in-situ treatment with lower cost,” says Kisan Mallesham Kodam, who was not involved with the study and is an Associate Professor of Biochemistry at the University of Pune. “Use of well-acclimatised plants and low cost material for construction makes these phyto-treatment units ideal for large-scale wastewater treatment,”

Govindwar and his colleagues are confident that their proposed design has practical relevance for bioremediation. Based on their findings from this study, they are developing plant reactors that can be combined with effluent treatment plants for neutralising industrial wastewater.

For the first time a study conducted by a team of scientist from Tata Memorial Centre, ACTREC, Navi Mumbai, revealed a distinct genomic alteration in tobacco and areca nut chewing Indian cancer patients. They suggest this genomic change can be used as a marker for timely prediction of oral cancer metastasis. The study was published in Oral oncology.

Paan, widely chewed by Indians, consists of areca nut (Areca catechu), betel leaf (Piper betel), slaked lime (calcium hydroxide) and tobacco. It is known to cause oral cancer. Humans develop addiction due to the presence of psychoactive chemicals resulting in mood upliftment and increased alertness. Tongue cancer, also called tongue squamous cell carcinoma (TSCC) is the most predominant form of oral cancer reported worldwide.

The cancer spreads first to lymph nodes around mouth region and subsequently to other parts, like, neck, lung and head. This phenomenon is called nodal metastasis. To prevent nodal metastasis in the lymph nodes doctors often have to perform a neck surgery and remove the primary tongue tumour along with 20-30 lymph nodes.

Improved treatment methodologies, like personalised therapy, where the drug specifically targets the specific genes or proteins present in the cancerous cells of patients have been unsuccessful in India. There are two reasons for this– first is the lack of genetic alteration data in Indian population and the second is the high cost of personalised treatment, ranging from 5-50 lakhs rupees.

“It is pertinent from Indian perspective to indigenously identify and validate the biomarkers present in Indian patients. Direct compliance of personalised medication designed in western countries is irrelevant for Indians,” says Amit Dutt, Principal Investigator of the study and scientist at Tata Memorial Centre, ACTREC. Currently, there are no biomarkers identified in Indian population that can distinguish between patients, who need neck surgery and those who don’t. As a result both are treated by surgery. An effective biomarker can spare 70% of patients from an unnecessary surgery.

In their search for an effective biomarker, the ACTREC team analysed the RNA expression profile of tumours from 253 tongue cancer patients. They found “five matrix metalloproteinase family genes, MMP10 to MMP14, being produced in higher amounts in tumour cells. Out of the five proteins, MMP10 showed an abundance in 48% tumour cells”, said Pawan Upadhyay, co-author and graduate student at Tata Memorial Centre, ACTREC. MMP10 is a protease– it can degrade the stabilising structure outside a cell and thus help in tumour spread and cancer progression.

The authors also analysed the tumours for the type of mutations. They found that the transversion (C:G > A:T) — a known hallmark of tobacco-associated cancer — was present in 53% patients. This indicated that tobacco was the most significant causal agent for cancer in the tumours studied.

“This study shows a clear advancement in the field of head & neck cancer research. Detection of MMP10 levels in tumour tissue or saliva may possibly be employed to identify patients who are likely to respond to MMP10 therapy and approved MMP10-inhibitors could be given to these patients as an adjuvant therapy,” says Bushra Ateeq, an expert in Cancer Oncology and Assistant Professor, Department of Biological Sciences & Bioengineering, Indian Institute of Technology, Kanpur.

Dutt and his team are now focusing their efforts on determining the threshold level of MMT10 that can distinguish patients who need surgery from those who don’t.“A histochemical analysis of 500 tumour samples with MMP10 is currently underway, to stratify the patients who could be spared unnecessary surgery. This clinical trial would establish MMP10 (if it qualifies) to be the missing biomarker in the field”, says Sudhir Nair, one of the authors of the study and a head and neck surgeon at ACTREC.

Standing in the middle of a dry lake bed, scientists drive a PVC pipe into the mud below, sometimes up to few meters deep, to collect sediment cores. Interspersed between grains of soil, are bits and bobs of preserved biological material. These have assimilated over hundreds and thousands of years and now serve as proxies for the past vegetation, land-use and climate. An ecological treasure trove of the region’s past, one might add.

Using this time-travel technique, researchers from the National Centre for Biological Sciences (NCBS), Bangalore and Indian Institute of Science, Education and Research, Mohali and Kolkata have reconstructed the ecological history of Banni – a mixed tree-grass (savanna) ecosystem in western India in Gujarat for the last 4600 years. “We hoped to understand what led to shaping today’s vegetation and where it might go in the future, based on what we can derive from the recent past,” says Jayashree Ratnam, from NCBS and one of the authors of the study.

Using a combination of indirect evidences - carbon isotope fingerprints of organic soil and microscopic silica crystals from dead plant tissues, the team estimated the abundance of trees and shrubs, relative to grasses. By measuring the ‘geochemical’ signature on shells of Cerithium snails, they assessed past rainfall regimes.

The team found that trees and shrubs dominated in this mixed tree-grass system of Banni between the last 4600 and 2500 years. Periods of high rainfall between these years potentially favoured this dominance.

Conditions became arid between the last 2500 and 1000 years and this time around, grasses emerged as the dominant life-forms. Researchers found frequent appearance of charcoal grains, which are basically burnt remnants of woody vegetation in the sediment cores, indicating recurrent fires during this dry phase.

It is in the same time period that evidences for pastoralism and settled agriculture start showing up in western India’s history. This period of grass-dominance and frequent fires was also accompanied by a greater abundance of grazing animals, most possibly livestock.

In the last 1000 years, the rainfall levels slowly increased and trees gradually began to make a come-back. But it is also likely that the escalated livestock numbers reduced grass abundance and additionally allowed for trees to proliferate.

“Our work suggests a cumulative role of climate and anthropogenic factors in maintaining the ecology of the Banni grasslands,” says Anusree A.S.from NCBS, the lead researcher of the study.

Kathleen Morrison, an expert in paleoecology and historical anthropology at the University of Pennsylvania, told IndiaBioscience, “This is a timely and important study. What’s most impressive is the range of analytical techniques used. It’s really cutting-edge work”. She added, “Tropical grasslands and savannas, although very large (both on a global scale and in India) and quite sensitive to climate change, are surprisingly understudied. We need a lot more studies like this in India”.

Like most other tropical grassland and savanna ecosystems, the Banni is predicted to experience recurrent droughts and increased human-use in the future. Given this knowledge of past ecological dynamics, a study like this has the potential to predict what the landscape will look like in the future and can inform management initiatives.

The study was published in the journal of Palaeogeography Palaeoclimatology Palaeoecology.

Artificial peptides that mimic fibrin, the body’s blood clot-forming protein, have been designed by researchers at IISER Kolkata and Saha Institute of Nuclear Physics.

Under lab conditions, the new “sealants” formed clots nearly twice as fast as fibrin, and were found to be safe to use with living cells. The sealants closely resemble fibrin’s make-up, but with added ingredients that confer durability and faster clotting.

“What we are aiming at is designing nature-inspired artificial sealants that are supposed to be better than what is available in nature, with the aim that it can be translated to clinics for handling difficult cases related to impaired blood clotting,” says Rituparna Sinha Roy, Assistant Professor, IISER Kolkata, who is one of the senior authors. Such sealants could prove useful during times of profuse bleeding such as traumatic accidents and battlefield injuries, or help patients who are unable to produce enough fibrin, the researchers say.

The study was published in Scientific Reports.

When blood spurts during an injury, a protein called fibrinogen is first converted to fibrin. Fibrin then forms long, tough threads entrapping blood cells and platelets into a mesh that hardens to form the clot. The clot’s structure is reinforced by interconnecting bonds that bring different fibrin strands together.

In one of the two sealants developed, the team constructed two strings of amino acids that bind together to form a fibrin-like mesh in the presence of a clot-forming enzyme. For added strength, the researchers inserted specific amino acids with opposite charges at matching sites on the strings to form strong interconnecting bonds. In another sealant, the researchers added amino acids that would make it resistant to peptide-cleaving enzymes.

Microscopic analysis showed that the sealants were able to form thread-like structures connected by nano-sized bridges and entrap blood cells, similar to fibrin. One of the sealants was able to trap blood cells almost twice as fast as fibrin. The sealants also showed greater stiffness than the functional portion of natural fibrin. Tests also revealed that they were not harmful to living cells.

The team also used computer models to analyze the 3D structures formed by the sealants. “We tried to mimic the physiological environment and see how these molecules will behave,” says Dhananjay Bhattacharyya, Professor, Saha Institute of Nuclear Physics, Kolkata, another senior author. The analysis gave them insights into how the sealants arrange themselves under simulated natural conditions, which could guide future design, the authors say.

“I think it is a good attempt to synthesize a peptide-based sealant to prevent bleeding, however, more experiments are needed to validate the adhesive in real life situations,” says Jayakrishnan, Professor, Department of Biotechnology, IIT Madras, who was not involved with the study.

Previously used artificial sealants such as fibrin glue have several issues, he points out. The components come from outdated human blood and bovine sources and care has to be taken to ensure their quality. “Fibrin glue is a 2-component affair and the sealant is not good for stopping bleeding from large incisions. It has poor mechanical and adhesive strength and large quantities are prohibitively expensive,” he explains.

Roy cautions, however, that the new sealants have only been tested in simulated conditions and not yet in animal models or clinical studies. The team hopes to collaborate with clinical researchers to test the sealants’ effectiveness further.

A piece of cotton fabric and four steel rods: that’s the prescription for corals suffering from Terpios Hoshinota infection, say scientists from the Pondicherry University in a new study published in PloS One.

Terpios is an aggressively growing sponge that forms black mats on coral surfaces. By 2010, 8 years after Terpios infection was first noticed in the South China Sea, nearly 70% of corals were killed due to Terpios outbreak. Similar accounts poured in from the Philippines, Japan and Indonesia. Buried in these reports were signs of a more pressing danger closer home.

Terpios was moving westward towards the Indian Ocean

At a rate of 11.5-23 cm/month, Terpios can cover squares of kilometres within a short time-span. This prompted a team of scientists from the Pondicherry University to investigate the matter. “Our motivation was clear–study Terpios invasion to manage reef protection,” says Thangadurai Thinesh, one of the authors of this study and postdoctoral Scholar at the Florida International University, Miami.

In 2013, researchers began examining Palk Bay, an unprotected shallow reef system in India for Terpios infection. They scraped sponge fragments sticking to coral surfaces for analysis. Both microscopy and genetic material extracted from the samples confirmed Terpios invasion in the area.

For the next two years, Thinesh and his colleagues carried routine surveys to understand Terpios’s growth patterns. Their field inventory shows that while Terpios grew by 9 folds, during this time 76% of the corals in The Palk Bay were destroyed.

“At that time, a research published by Chaolun Allen Chen of the National Taiwan University showed that Terpios accumulates large amounts of cyanobacteria at its edges, when invading corals” recounts Thinesh.

Cyanobacteria use sunlight to produce food, much like plants. The researchers posited that this extra bolus of energy from the bacteria could be fuelling the sponge’s expansion. If that were true blocking photosynthesis should stop Terpios in its track.

To test their idea, the researchers placed cotton hoods to filter the sunshine over five infected coral colonies and monitored sponge growth. Initially, there was no visible difference in Terpios growth in naked and covered corals, But after 10 days, in corals shielded from the sun, the Terpios started losing its colour. Tests show that amount of chlorophyll a – the pigment that helps cyanobacteria make food- was halved in sponge samples retrieved from covered corals. This can account for the loss in sponge colour. Scientists also noticed a visible growth retardation of Terpios in covered colonies Unable to perform photosynthesis within the hoods, a huge fraction of cyanobacteria let go of Terpios’s surface. With its nutrient making factories gone, the sponge could no longer sustain its onslaught explains Thinesh.

The growth halting effect of cotton hoods was effective for an entire year. By May 2016, when scientists performed their last field study, the corals kept under a hood for 10 days showed no additional Terpios growth even when the hoods were removed. Additionally, the chlorophyll content in the existing sponge mats was also reduced by ten times.

However, Jih-Terng Wang, a member from Chen’s lab expresses concern. “It is technically impossible to build the shading facility on the reef,” says Wang. “This method might work when Terpios infection just begins and the size of the patch is small”.

Thinesh agrees: “Shading is not feasible on a large scale, but it could be effective to conserve critically endangered species if we find the Terpios invasion before it is established,” he adds.

Thinesh and his team are now looking at other bacteria and their role in Terpios expansion “Understanding Terpios larvae ecology and its spreading dynamics will help in managing the infection in the long term”.

At the recently organised 'Careers in Science' workshop the myth that PhD-Postdoc-Principle Investigator (PI) is the only career path for science graduates was dispelled completely. The workshop was co-organised by Division of Biological Sciences, IISc and IndiaBioscience

K. VijayRaghavan, Secretary of Department of Biotechnology, who addressed the participants over Skype challenged the notion of ‘mainstream’ and ‘alternative’ careers in science, adding that such distinctions are irrelevant in the current era. The PI-career path has become a tradition for the lack of awareness on other diverse roles scientists can engage in.This lop-sided view on science careers is now being corrected as more and more scientists tread new avenues, inspiring others to make their own trails.

Some such career options discussed at the workshop are- a start-up entrepreneur who solves relevant problems through out-of-the-box innovations; technical support specialist in a company to complement the sales and marketing departments; project manager in government or private programme; NGOs working to create a sustainable interface between laboratories and the rural population; intellectual property, technology transfer and law.

Umesh Varshney, Chairman, Division of Biological Sciences, IISc said, contrary to popular view, even these non-conventional careers require intimate knowledge of basic scientific concepts, first-hand experience of solving problems, ability to manage a team – all being integral components of PhD training.

So, how does one prepare to enter these avenues after a PhD? “Know thyself” – This old adage was endorsed by the event's speakers.

Talking about her experiences, Fathima Benazir, Cofounder and CEO, Azooka Life Sciences, said, all she wanted was “to keep publishing in higher impact journals”, until a friend asked her, why was she working hard on discoveries, only to bury them in books? This question eventually led her to develop a product from long-forgotten observations made during her PhD. Today Azooka Life Sciences is the only company in the world to produce a food-grade DNA staining dye. Good riddance EtBr! Benazir is convinced her start-up experience has been more satisfying than her stint in the lab solving complex, esoteric problems.

A similar realisation propelled Swati Subodh, to step out of the confines of “air-conditioned labs” towards building bridges that directly transfer the fruits of scientific labour to underprivileged people. Her brainchild, IMIB (1 Million for 1 Billion) foundation, works across scientific and engineering disciplines to make effective health care accessible to the rural population. Here again, self-realisation – knowing what she wanted to achieve with her degree- was her first step towards a paradigm shift in her career.

Another speaker, Rajesh Nair, CEO Basil Biosolutions, talked about how sales and marketing can be an interesting path for those with good people skills. As he concluded his talk, he was able to convert a few audience members, from being not interested in sales to wanting to pursue it as a career.

Lipika Sahoo, CEO of Life Intellect and an alumnus of Division of Biological Sciences, IISc, talked about the various aspects of intellectual property and the need for scientists to engage with it.

In an insightful lecture, Shyam Suryanarayan, Founder and CEO, C:\Drive, talked about the skills industry looks for when hiring people branching out of academia. He advocated an “inside-out” approach to looking for jobs. Identify your area/organisation-of-interest. Research this non-academic field, like you, would a problem in the lab. Who are your potential employers? What skill-set do they require in their employees? How would you fit into their team? Once you have done your homework, go ahead with building connections with experienced people on professional platforms; attend seminars/workshops for exposure to relevant skills; engage people by requesting for “informational interviews” on how to make a headway into a new field. All these steps form the core of career preparedness; to begin well is a job half-done.

The final speaker, Taslimarif Saiyed, CEO, C-CAMP, summed up the common message that each talk relayed- irrespective of whether you are a fledgling or a seasoned scientist, firmly rooted in academia or elsewhere, use your scientific training to innovate, collaborate and challenge yourself by moving out of your comfort zones to achieve what you dreamt of at the dawn of your career. He added, that now is a great time to get into science entrepreneurship as there is plenty of government support available for such ventures.

As a postdoc at IISc facing the dilemma of how to carve a career in science away from the bench, I found the workshop to be a revelation of sorts. Now, the future doesn’t seem so uncertain after all. I can already envision a time when many of us would look back on this workshop as the catalyst that kick-started our journey towards ‘self-discovery’.

Nanoparticles of curcumin (principal bioactive component of Turmeric) have the potential to reduce liver toxicity induced by anti-tuberculosis drugs and prevent reinfection of tuberculosis (TB), says a study published in the journal Frontiers in Immunology.

The study was initiated by Santosh K. Kar, Professor, School of Biotechnology and his team at Kalinga Institute of Industrial Technology (KIIT). So far, curcumin’s potential as a drug was hindered due to its low bioavailability— it was poorly absorbed by the intestinal lining, followed by its rapid metabolism and quick elimination from the body.

Kar and his team synthesised curcumin nanoparticles measuring ~200nm in size. “Nanoparticles of size smaller than this will enter cells, interfere with their metabolism, and may result in toxicity. We used a surfactant to prevent aggregation of the nanoparticles. Our nano-formulated curcumin shows five times greater bioavailability and enhanced half-life than normal curcumin, when injected intra-peritoneally into mice. Enhanced stability and non-toxicity make it possible to administer curcumin in large doses (upto 8g/day) to humans,” says Kar.

Further work on nano curcumin to demonstrate that it can be used as an adjunct drug along with isoniazid (INH) for TB therapy was conducted by Gobardhan Das, Professor, Special Centre for Molecular Medicine, Jawaharlal Nehru University (JNU) and his team then at International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi.

INH is one of the first line drugs used for TB therapy. Curcumin is a known anti-inflammatory and antioxidant chemical. In this study, when mice infected with TB were treated with INH coupled with nano curcumin, they showed increased clearance of Mycobacterium tuberculosis (M. tb) infection, as compared to mice treated with INH or nano-curcumin alone. This means that curcumin provides greater immunity, which in turn means reduced duration of therapy. The study team also found that animals previously treated with nano curcumin were resistant to M. tb infection, whereas animals treated with only INH were frequently prone to reinfection by M. tb.

Animals that received both INH and curcumin showed increased levels of T helper type 1 cells (Th1) than those that received only INH, indicating increased host immune response. Prolonged therapy with INH is shown to induce apoptosis in Th1 cells. Curcumin seems to prevent this, both in vitro and in vivo, and restores antigen-specific T-cell proliferation.

India is struggling to control TB through the Directly Observed Treatment – Short course (DOTS) program mainly because a large number of patients abruptly discontinue therapy. The most common reason for this is the liver toxicity induced by the first line therapeutic drugs- INH, rifampicin and pyrazinamide. Curcumin’s antioxidant properties endow it with hepatoprotective function, as seen in a previous study. The current study found that curcumin reversed liver toxicity induced by INH in mice, observed through both macroscopic analyses and liver function tests.

TB as a disease, challenges the body through two routes: microbial infection and inflammation. Curcumin, having both anti-microbial and anti-inflammatory functions, has proven itself as an ideal choice for therapy. This may well be the elusive cure for multi-drug and extensively-drug resistant of TB. Kar is also confident of curcumin’s ability to treat other diseases, “many studies using animal models have shown curcumin to be effective against some kinds of cancer. We would like to use it in patients suffering from arthritis, neurodegenerative diseases like Alzheimer’s and Parkinson’s, as well as in cerebral malaria where no effective drug exists.”

However, there has been great opposition to curcumin being hailed as a wonder drug. The most recent instance was earlier this year, when a new report by Kathryn M. Nelson and her team from University of Minnesota caught everyone’s attention as it rubbished claims of curcumin’s therapeutic potential. The report declared that no double-blinded, placebo controlled clinical trial of curcumin had been successful. Nelson’s team also went on to add that curcumin is chemically unstable under physiological conditions of pH 7.4 and 37°C, hence falling short of the primary requirement of most therapeutic molecules. Curcumin’s pharmacokinetic parameters also came under the scanner as the team quoted instances where curcumin remains undetected in the serum of test subjects, despite dosing at ~12g/day. Nelson has highlighted the fact that while curcumin is considered as a dietary supplement by most, the FDA does not support its use as a therapeutic.

Unfazed by criticism, Kar is hopeful about curcumin’s potential. He says,“curcumin has been used in our traditional system of medicine for a long time and therefore cannot be written off without proper investigation. We have published a study showing how curcumin bound to chitosan nano particles can cure malaria in mice. Govindrajan Padmanabhan, former director, Indian Institute of Science (IISc) has been trying to develop an Artether-Curcumin combination therapy for Malaria treatment. We have also shown how nanocurcumin can prevent heart atrophy under hypoxia conditions.”

Referring to Nelson’s report, Padmanabhan lists down possible reasons for the severe opposition, “Although more than 100 clinical trials have been carried out, including 70% of them being against cancer, detailed large-scale double-blind studies have not been carried out. Preparations of curcumin used the world over are not 100% pure. Detailed studies on each of turmeric’s components are not available. In addition to all these, there is an inherent bias against traditional molecules, although FDA has opened up for the use of such therapies with adequate proof.”

Padmanabhan in his forum article hypothesizes that curcumin may offer protection through immunomodulation of the host response, rather than killing a particular pathogen. To clear the doubts raised against curcumin’s beneficial effects, he suggests conducting clinical trials with select infectious diseases where curcumin can be used as an adjunct drug to standard therapy. He further adds, “The results of such trials can be seen clearly in a short time, unlike cancer where there are complex changes for extended periods of time, providing a definite conclusion on curcumin’s efficacy. For example, malaria therapy is only for 3 or 5 days.”

Padmanabhan welcomes the results of Kar and Das’s study, “I believe that the M. tb antigens generated by INH-mediated killing, in presence of curcumin (even if it is present transiently), can create immune memory leading to long-term protection. Further studies will help understand this better.”

The researchers have their future task cut out. “After efficacy studies in mice, we have to get approval for testing curcumin as a food supplement in humans. Following that, we can get clinicians to prescribe it to a few TB patients with informed consent. If results are positive, the trial can be expanded to a larger number of patients.” says Kar.

Good teaching is more a giving of good questions than a giving of good answers. -Josef Albers, artist and educator

The art and science of being a good teacher often comes with the ability to ask good questions. That is the take-home message from a recent study in the journal CBE-Life Sciences Education; the type of question—how a question is framed—can tell educators a lot about student thinking on the concepts being taught.

Exam questions are either open-ended or closed-ended. Closed-ended questions such as multiple-choice, multiple-true-false, etc. are easy to grade, do not depend on student writing skills or suffer from grading inconsistencies (where different graders assess answers differently). However, open-ended questions like free-response (which require essay-type answers), short answers, diagramming, etc. are particularly good at capturing student thinking since the students must construct answers rather than simply choosing them.

This study by Hubbard et al. was carried out during an introductory biology course at the University of Nebraska–Lincoln, on a total of 405 students. The students were exposed to multiple-choice, multiple-true-false- and free-response type questions throughout the course to familiarize them with the formats, before being asked to take four unit tests for assessments. Each multiple-choice and multiple-true-false question stem was followed by four statements, one of which had to be chosen for the former, while each statement had to be marked as ‘true’ or ‘false’ for the latter. In each of the tests, students were asked eight multiple-choices and 10 multiple-true-false questions that were common for all students. Each test also contained four experimental questions that were presented either as multiple-true-false or free-response questions, with almost identical question stems, except for minor adjustments in syntax or additional prompts for free-response questions.

For experimental questions, each of the four statements in the multiple-true-false format represented a part of the expected answer to the corresponding free-response question. Based on whether students addressed the concepts represented by these statements in their answers, assessors could score parts of free-response answers as ‘correct’, ‘incorrect’ or ‘unclear’ for each corresponding multiple-true-false statement. An ‘unclear’ code was used when a student either gave an ambiguous answer, or because the concept corresponding to that multiple-true-false statement was not addressed in their answer.

When student responses to the experimental questions were analyzed, the researchers found that although more students provide higher numbers of correct answers for multiple-true-false questions, correct response rates across the two question formats were highly correlated.

“Our main findings were that each format has particular strengths and limitations and that instructors should keep these question tendencies in mind when designing tests and interpreting results. By asking students to evaluate specific statements, multiple-true-false questions can uncover incorrect ideas that may go undetected in the free-response format,” say authors Brian Couch and Joanna Hubbard. “However, multiple-true-false questions tend to overestimate the frequency of particular conceptions, while free-response questions require students to put their thoughts in their own words and thus provide a more unfiltered portrait of student thinking,” they add.

When presented with multiple-true-false questions, 33% of students could classify all true/false statements correctly, while 66% gave a combination of incorrect and correct statements, revealing that they had mixed conceptions. Free-response questions produced a wide array of patterns based on combinations of correct, incorrect and unclear answers—only 9% gave fully correct answers, addressing all four conceptions. The majority of free-response answers—58%— were a mix of correct, incorrect and unclear conceptions and a fairly large subset of students (29%) also provided answers with no correct elements, consisting of wholly unclear or unclear and incorrect answers.

In all, though multiple-true-false questions are useful in judging how students tackle specific concepts, they can also obscure nuances in student thinking. Since multiple-true-false formats require students to simply state if a statement is correct or not, and not construct their own answers, unclear concepts are simply not detected.

Free-response questions on the other hand, may provide a more reliable estimate of student thinking, but are limited in their ability to identify the specifics of incorrect conceptions. For example, if a student is unsure of a particular conception, he or she may not write about it, or else might provide unclear answers that make it difficult for an assessor to identify specific problems in understanding. Furthermore, the study also indicates that the free-response format has extremely low diagnostic value for lower-performing students, since most of their answers tended to be unclear.

Considering these tradeoffs, teachers must choose the appropriate questions types or mix question types to assess students. Narmada Khare, who teaches biology to undergraduates at the Indian Institute of Science, Bangalore, agrees with the mixed-question type solution. “I think that question papers should have a combination of free-response and multiple-true-false questions,” she says. Khare believes that although multiple-choice-questions and multiple-true-false formats are very practical choices, especially for evaluating large numbers of students, free-response questions are important too. “Multiple-true-false and multiple-choice-question formats do not improve a student’s ability to express himself or herself, a skill that is essential in a scientist,” she adds.

The study therefore leads one to conclude that when evaluating students, it isn't a matter of ‘asking the right questions’; instead, the challenge lies in asking questions the right way.

Thomas Pucadyil, faculty from IISER Pune, is the only Indian scientist to be awarded the HHMI International Research Scholarship this year. Out of 1400 applicants, including Pucadyil, 41 scientists from 16 countries won this prestigious award. His lab studies how cells produce vesicles.

Q. Why is it important we know about how cells produce vesicles?

This process impinges on practically every aspect of cell physiology. The intricate distribution of organelles you see displayed in Cell Biology textbooks — is maintained that way by the dynamic production and consumption of vesicles.

Anytime you starve cells of essential nutrients, these organelles either change their shape or disappear entirely. To maintain organelle shape and identity, cells need to produce a continuous stream of vesicles. For all the progress we have made in this field, we still don’t know enough about where or how the vesicles for forming organelles arise.

Q. Could you give us a summary of research in the field -- what is known, and what are some of the open questions?

The simplest forms of life that developed on early-Earth, invariably ended up encased in a lipid bilayer. In high school and college Cell Biology courses, students learn about the many features of the bilayer - that it is selectively permeable, very flexible — easy to bend and twist, but extremely difficult to rupture. The same reason that makes it choice substance for containing life forms, also makes it difficult to ferry membrane proteins from one part of cell to another. The vesicular transport system is believed to have evolved because membrane proteins can’t be transported like soluble proteins. To move them, part of a membrane has to bud-out as a vesicle which ultimately fuses with another (target membrane).

The field knows a lot about possible fission catalysts. It’s kind of funny in that practically everything we know about fission has come from studying dynamin, a protein involved in budding vesicles from plasma membrane.

The counterpart of mammalian dynamin protein in fruit fly is called shibire. The name translates to “limbs gone to sleep”; for a remarkable limb paralysis seen in Shibire mutants. AT 27 deg, this fly looks just like any other; but when taken to 34 deg, it collapses with sudden paralysis. What’s even more remarkable is that when you bring it back to 27 deg, the fly returns back to normal- flying about as if nothing happened! It is very rare to get such a ‘full circle’ phenotype. We know now that the reason this phenotype is seen is because the mutation prevents the formation of neurotransmitter vesicles. And since that process is so rapid, you can see the phenotype in such a short period of time.

Ever since these reports, dynamin has been the gold standard for other proteins involved in fission. This protein has a GTPase domain. If you scan the genome for other proteins that also have the [GTPase] domain, you could find other candidate proteins involved in membrane fission. This is what’s called a “candidate-based approach”; you are only likely to find something like dynamin. That’s one of the reasons we decided to not take that approach. Rather we devised an assay where we score for fission activity, in our hope to expand the repertoire of molecules involved.

We want to figure out a “parts-list”, which are the molecules involved in budding vesicles out of membranes; with the hope that if you figure out enough of them, you could draw generalisations on how the process works. We start with highly simplified model systems where we figure out the process of budding of vesicles.

Q. How does your lab study formation of vesicles?

In my lab, we have devised a new method to study membrane fission. The traditional method of studying membrane fission is very laborious. It uses polystyrene beads trapped inside an optical trap. If you touch the bead to the surface of a large vesicle and draw it back, you pull out the membrane in the form of a tube. When I started, this was all there was available, in the form of technique. I did not want to go down this route because it is not trivial at all. It requires a lot of time and effort, and the best-case scenario is you end up with one tube. We wanted an assay system that gives us an array of [membrane] tubes; something that’s robust; doesn’t require elaborate technical expertise and is amenable to downstream fractionation approaches. So these were our motivations behind developing a new assay.

Our method to make membrane tubes requires a small amount of lipid and is relatively easier. We call these supported membrane tubes (SMrTs). To start, you coat a glass coverslip with polyethylene glycol or PEG, the reason being that membranes stick to glass very well and that would cause a membrane tube to collapse. On this coated coverslip, we spread some lipids. Once dry, the coverslip is placed inside a flow cell. When exposed to buffer inside the flow cell, lipids self assemble to form a membrane that takes the shape of very large vesicles. We then flow buffer to extrude these vesicles into long and narrow membrane tubes. The outcome is that you see hundreds of these tubes arranged parallel to the flow of buffer. Proteins of interest are then passed onto these tubes and fission is observed as tubes getting cut. This high-throughput system can be assembled in a matter of minutes and is highly reproducible. (Watch a video of membrane fission on Pucadyil Lab website).

Q. How was the idea of supported membrane tubes conceived?

The bulk of my PhD (at CCMB Hyderabad) was spent studying membrane proteins. Close to finishing, I was thinking about getting into reconstitution biology - make your own membrane, add your protein of interest and see if it shows anything interesting. My first foray into reconstitution biology started while I was still at CCMB. By then I knew how to play around with model membrane systems. With that technical expertise I went to The Scripps Research Institute for postdoctoral training, where I studied membrane fission. The first model membrane system to study fission came out of my work there. In my lab at IISER, we built upon this work.

Q. Could you tell our readers the process of selection for HHMI International Research Scholarship?

The grant is for five years. The entire application period was 6-9 months (till interview). The application itself was very straightforward; does not emphasize on an elaborate proposal. They fund very diverse types of applications, which are reviewed by an international panel.

The interview took about 30-45 minutes during which they asked about experimental details of the proposed research; where you see yourself in 5 years, etc. There were also questions about support system at your institute - ambience and facilities; as well as internal process of evaluating faculty.

Q. In a previous interview, you attributed your desire to pursue a research career in Biology to a summer rotation experience. What would you say, can be done to kindle this enthusiasm for research in students?

A formal set-up for education is necessary. But for most students, their exposure to science is predominantly reading textbooks and research articles, about what discoveries others have made. Sadly through this process, we end up deifying laureates, but we don’t tell enough about doing science. As a result, the process of doing science can seem very distant.

It was no different for me, until I did the summer rotation at Amitabha Chattopadhyay’s lab at CCMB (where I would end up doing PhD). It was during this time that doing science seemed within reach.

I think it is crucial for students to have some independence in studying science, much before PhD. This is critical not just for doing research, should they so choose in their future. Education in science should give them tools for any kind of future they desire.

Did you ever think, a modest vegetable in your sambhar, could be a part of your dental fillers or healing bandages? According to a new study by Scientists from Vivekananda College of Pharmacy, Bangalore and IISc, Bangalore, ridge gourd’s fibre can be used to make lignin nanoparticles (NP) that can be used as an excipient for tablets and capsules, to tether drugs for a sustained release or even for targeted drug delivery. The study was published in Industrial Crops and Products.

The Indian ridge gourd [Luffa cylindrica] is a dark green vegetable with white pulp on the inside and hard green surface on the outside with ridges. The idea of making an NP from a local vegetable struck a chord with the researchers as they were looking for a raw material that had "high lignin content, was readily available and inexpensive,” says Anupama Rangan, Professor at Vivekananda College of Pharmacy.

Lignin is second most abundant constituent of the cell wall of vascular plants, after cellulose and provides a protective barrier from saprophytic and pathogenic microbes. Its complex polymeric structure; consists of several non‐phenolic phenylpropanoid units making −it a hard nut to crack. It is recalcitrant towards chemical and biological degradation methods. Researchers have used acid hydrolysis, alkaline hydrolysis, delignification via oxidation, organo-solvent and ionic liquids pre-treatments to break the lignin-cellulose complex in other plants. Surprisingly these extreme methods did not give desired result.

Not going the chemical route, this group of scientists chose to use enzymes to extract lignin from the gourd. “We were inspired to use enzymes for degradation of lignocellulose as enzymes are specific, require mild conditions for reaction and avoids the use of toxic and hazardous reagents, tending towards green chemistry”, says Rangan.

The team used enzymes from wood-degrading fungi and bacteria who use them to degrade the lignin in the wood and derive energy. It “cleaves the cellulosic parts away, to facilitate the separation of lignin-rich parts” says, Reghu Menon, Professor, Department of Physics, Indian Institute of Science, Bengaluru and one of the authors of the paper.

Lignin being full of aromatic rings needs temperatures as high as 600⁰C to decompose. However, enzymatic conversion of macro and microscopic lignin into nanostructures occurs at 55⁰C. These NP are biodegradable, non-toxic and obtained from renewable material.

Annama Anil, Assistant Professor at DBT-ICT (Institute of Chemical Technology), Centre of Energy Biosciences, Mumbai working on Design & Engineering of enzymes and unrelated to the study says “their use of chemicals and enzymes in making the nanoparticles is not justified. There are many easier methods by which they could have obtained similar results. But may be their need to obtain specific dimensions for the nanoparticle, have made them use the enzymatic method”.

Meanwhile, Rangan and colleagues are working on a pilot to scale up the production of the lignin NP. “The commercial enzymes are expensive; we plan to use immobilised enzyme systems or develop in-house recombinant enzymes to reduce the cost. The use of continuous or batch reactors with immobilised enzymes along with in-situ isolation of nanoparticles, as a continuous process will definitely have commercial advantages”, says she.

In a new study published in Scientific Reports, scientists describe a new method to precisely identify a class of plant sucking pests which affect several commercially important crops.

Thrips are tiny plant sucking insects, one to three millimeters in length that cause damage to crops by direct feeding and by transmitting plant viruses. At present, these insects are identified based on their physical features like color and body architecture. A major obstacle in correct identification is their small size and high degree of similarity at some stages of their life cycle. Identifying these insects correctly is important for designing appropriate pest management strategies.

Now scientists at the Centre for DNA Taxonomy, Zoological Survey of India in Kolkata, have developed a DNA barcoding technique to identify thrips insect species in India and found that this technique is effective. It could be of immense value as thrips cause huge losses to crops such as onion, chilli, brinjal, capsicum, watermelon and tomato. Identifying thrips correctly can help design relevant pest management strategies to prevent these losses.

Researchers collected 336 insect samples from 78 locations in India. The sample collection was done for 4 years between 2011 and 2015. In 3 years, they have made a library of 370 DNA sequences that can be used for precisely identifying these plant pests. DNA analysis was done to analyze the sequence of the mitochondrial cytochrome oxidase gene, said Kaomud Tyagi, who is the first author on the study.

“We have standardized and confirmed DNA barcoding method to be used for identifying thrips species correctly. Our study has also revealed that similar looking insects can belong to different species. Identifying species of thrips is now possible at the larval stage or even from a small portion of the body”, said, Vikas Kumar, a member of the research team.

Thrips also leave white streaky trails after feeding on fruits making them unfit for exports. In the long run, using DNA barcoding for identifying thrips could help increase income from exports, believes Kumar. The study will help design appropriate pest management strategies as different species respond to different pesticides and doses.

Sharad Mohan, a scientist at the Indian Agricultural Research Institute, New Delhi, who is not connected to the study agrees. He said, “barcoding is of immense value in validating the diversity of pests in different agro-climatic zone of India. Instead of using conventional taxonomic ways that may take months, barcoding helps in identifying pests that helps recommend and implement specific management protocols without wasting much time."

Kailash Chandra, Director of ZSI, said “we are starting a new project on large scale barcoding of insect pests and vectors of agricultural and veterinary importance soon”.

This article was originally published by India Science Wire.

Development of tauopathies—a special class of neurodegenerative diseases—in Drosophila, resembles its development in humans, much more closely than previously thought, says a new study by scientists at the Department of Genetics, University of Delhi. The study was published in the journal BBA-Molecular basis of disease.

Contrary to previous studies in fruit flies, this team found neurofibrillary tangles (NFTs) in Drosophila, when the flies were artificially induced to produce wild type and mutant forms of human tau protein. Tau is a microtubule-associated protein, which plays a critical role in tauopathies, which are characterised by hyperphosphorylation of tau and its subsequent deposition in the brain as NFTs. Some commonly known examples of tauopathies are Alzheimer’s, dementia, and Parkinson's disease.

Drosophila has been used as a model organism to study human neurodegeneration for quite some time, however, neurofibrillary tangles had not been reported before. “This study suggests that tau pathogenesis via NFT formation is (evolutionarily) conserved in Drosophila and humans”, says Surajit Sarkar, assistant professor, Delhi University and principal investigator of this study.

The team of researchers introduced genes expressing wild type or mutant forms of human tau (h-tau) in Drosophila and studied their expression in the neuronal tissues. They observed Drosophila larval eye discs and adult eye sections to understand the phenotypic changes brought about by h-tau. In the eye sections of 5-day old adult flies, both wild type and mutant forms of h-tau showed signs of mild to severe human neuronal tauopathy. Higher magnification analysis of h-tau aggregates revealed presence of NFTs, with morphology similar to what Alois Alzheimer had originally described. “Drosophila h-tau models so far were regarded as NFT-free models and several studies have been performed based on this inference. Hence, we had to be extremely careful while designing our experiments and interpreting the data. We had to include several experimental replicates to decisively demonstrate the NFT-mediated pathogenesis of human tauopathies in Drosophila,” says Sarkar.

Additionally, it was seen that the incidence of these NFTs was heightened around degenerated neuronal tissues. A linear correlation was seen between the amount of flame-shaped (advanced stage) NFTs and severity of the disease.

The most interesting finding of this study is the relationship between NFT formation and expression of the gene dMyc ( Drosophila homolog of human c-myc proto-oncogene). In larval eye discs, h-tau expression increased when dMyc was selectively upregulated in cells expressing wild type h-tau. Additionally, tissue-specific down regulation of dMyc by RNA interference reduced NFT formation. The important conclusion of this study was that aggregation of hyperphosphorylated and normal tau as NFTs resulted in pathogenesis and neuronal death in Drosophila models of human tauopathies, and that regulating dMyc expression was one way of neuronal rescue.

Commenting on this study, Upendra Nongthomba, associate professor at Indian Institute of Science (IISc) who heads the developmental and biomedical genetics lab says, “Drosophila as a target model provides flexibility to study any kind of diseases. Regenerative or curative studies may need higher vertebrate models. Most importantly, however, NFTs can be studied more for information on suppressors and enhancers, to enable screening of drugs.”

Sarkar indicates possible follow-up studies involving large-scale screening of potential drug molecules and gene modifiers that can control NFT formation. This study may have involved just a glimpse into the Drosophila eye, but has carved out a whole new vision for the future of neuroscience.

Chromatin from dying cancer cells causes DNA damage and inflammation in healthy, non-cancerous cells in their vicinity, says a recent study published in Cell Death Discovery. Circulating cell-free chromatin (cfCh) may thus play a role in metastasis and spread of cancer, both locally and in a systemic manner.

The study, conducted by researchers from Advanced Centre for Treatment, Research and Education in Cancer (ACTREC) at Tata Memorial Centre, Mumbai and Homi Bhabha National Institute, Mumbai reiterates findings of their previous study, which demonstrated that fragmented DNA and chromatin are biologically active molecules. Chromatin from cells of cancer patients as well as healthy volunteers was shown to damage surrounding healthy cells by integrating into their genomes causing double-stranded breaks and apoptosis.

The researchers used dead cells from a cancer cell line (called Jurkat), which had its chromatin labelled with a fluorescent molecule-Bromodeoxyuridine (BrdU). They incubated these cells with an actively growing cell line (NIH3T3). BrdU is used to study cell proliferation since it is incorporated into the newly synthesised DNA of replicating cells. In this study, the authors detected fluorescence in the actively growing cells after 6 hours. This indicated that nuclear material (chromatin) from the dead, cancerous cells was taken up by the live cells. When the same cells were treated with chromatin degrading agents no chromatin uptake by actively growing cells was detected. The live cells also showed evidence of DNA damage response, inflammation, and apoptosis.

The next series of experiments consisted of injecting fluorescently-labeled dying cancer cells intravenously into mice to see if a similar response is elicited in vivo. Fluorescent signals were detected in brain, lung, and liver cell nuclei of the injected mice, thus showing the presence of cfCh in the cells of these distant organs. Evidences of DNA damage and inflammation were also detected in these organs.

The researchers were eventually able to show through both in vivo and in vitro experiments that CfCh enters healthy cells and integrates into their DNA.

What does this mean for cancer therapy? Indraneel Mittra, cancer surgeon and the principal investigator of this study says, “this suggests that metastasis may be caused by circulating dead tumour cells via the medium of chromatin fragments. This challenges the well-established theory of cancer metastasis that living circulating tumour cells (CTCs) get lodged in distant organs and grow to form secondary tumours.” He further clarifies, “most CTCs are apoptotic and patients whose CTCs are enriched in apoptotic cells have poor prognosis and have a greater tendency to develop liver metastasis.”

Does this mean that assaying levels of cfCh in a cancer patient can help assess the degree of metastasis? It is a long way off but it may be a possibility in the future. It will require us to “design a method, which can distinguish DNA from cancer cells from those released by normal cells, perhaps by making use of an epigenetic marker that distinguishes transformed cells from normal ones”, says Vaijayanti Gupta, Vice-President, Clinical R&D, Strand Life Sciences. “Once this is established, one has to figure out if one has to look for them in the CTCs, or pockets where cancer cells are known to hide, like the thymus, or just free-floating fragments in the plasma”, she adds.

“Our paper suggests a re-thinking of ‘kill cancer cells at any cost’ approach”, says Mittra. “It may be that the more we kill, the more we may be helping it spread. Therefore, future research should be focused on destroying the chromatin fragments that emerge from dead cancer cells thereby preventing further spread,” he concludes.