Technology Transfer: A Pathway of Commercializing Research

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TechTransfer!

In the world of academic research, in order to be regarded as ‘productive’, paradoxically speaking, one needs to publish or perish. Although this idea has been floating around since ages, in the current era it does not seem to be enough just to publish and expect your work to get noticed. Beyond the scholarly publications, there is a whole new cosmos where some one not just notices the discovery but also channelizes it to develop into a tangible product that ultimately reaches the consumer. This entire process in which the knowledge is passed on from an academic institution to an industry is known as Technology Transfer. It is a pathway through which findings from fundamental and application-based research are advanced to commercially relevant applications via industries. Research from the lab desk to the market is made possible with the bridging provided by a team of experts who manage the commercialization aspect of research by identifying and evaluating suitable technological developments, file patents, negotiate license agreements along with routine review of similar on-going projects. This coordination is a vital aspect of technology transfer to ensure efficient and smooth exchange of intellect between researchers and potential manufacturers. This academic-industry partnership therefore requires a team that could function as a link between the two to promote the flow of work from laboratories to successful business enterprises.

With an esteemed team of leading scientists and growing scientific community, JNCASR over the last couple of years has been accelerating its progress w.r.t. commercialization of academic research. Having said that, for equipping this scientific community not just with financial support but with technological and legal assistance as well, JNCASR established its Technical Research Centre (TRC) in 2016. TRC, by design identifies such projects and teams at the institute that possess the caliber to translate their research ideas and experiments to sustainable and palpable products and technologies that aims to improve public health, environment and economy.

Prof. K.S. Narayan, TRC Coordinator, Dean R&D, JNCASR
Prof. K.S. Narayan, TRC Coordinator, Dean R&D, JNCASR
Dr. Kripa Jalapthy
Dr. Kripa Jalapthy
Sourabh Gargav
Sourabh Gargav

Through several formal and informal cooperation between technology developers (as in the researchers) at the institute and the technology seekers (as in the entrepreneurs/manufacturers/industrialists either in public or private sector); this team of TRC marches towards bringing the two platforms together in order to tunnel in the science done at the desk to reach out to the common man. Recognition of such areas is extremely relevant for they need proper guidance, counseling and financial support to scale-up the emerging technology at the lab to being innovative and ultimately an established technology. TRC team encourages such research at the institute and primarily manages this interface work through building contacts with potential companies, arranging formal meetings between scientists and company personnel and most importantly protects the intellectual property through patenting/copyrighting and licensing the novelty of research. The later is done during formal transfer of rights to companies/industries to use and commercialize the research product. In simple words, TRC encourages, guides and supports researchers, actively bolsters their work to find suitable collaborations with industries to use and commercialize new technologies developed at JNCASR to eventually benefit the society.

Exercising this process in years to come shall aid the progress of the institute via gaining recognition and reputation for its innovative research potential.  Moreover, building a path for research to reach out for greater benefits of the society in terms of health, environment and economy is the primary motive behind formation of this department. In particular, the team plays a pivotal role in helping researchers realize the potential of transferring their new discoveries or technologies out of the lab benches to the hands of industries/companies to test the mass scale production and aim to market their innovation. This process otherwise would be in a precarious state for taking a step ahead both by scientists and industrialists to come to a decision of examining lab research outcome at an industrial level.

Currently the team of TRC is headed by Prof. K.S.Narayan, Dean R&D and is run by Sourabh Gargav and Dr. Kripa Jalapathy who strive to make academic research and industry shake hands. Feel free to reach out to this team if you have some interesting results that is unique and significant to have a commercial value or a fantastic innovation that is directed towards answering or dealing with major concerns of the society.

This is first among a series of articles about the importance and reach of Technology Transfer through TRC at JNCASR. Keep reading to know more!

The article is authored by Manaswini Sarangi, Evolutionary Biology Laboratory, EIBU, JNCASR.

Cover Art by: Manaswini Sarangi.

If you were to function as a cell, what type would you be?

Insight from work on Rudhira
Insight from work on Rudhira

Imagine having the supreme ability of transforming yourself to any other functional being of your choice with impeccable precision, just like Mystic from X-men (Marvel fans would get the hint)! Setting aside Sci-Fi, in fact if we take a look inside us, each of us do have such remarkable cells in our body that carries immense potential (although choice is not conscious) to develop into a variety of structurally and functionally diverse cell types, especially in the early stages of life (embryonic stage) as well as during the growth phase. These gems are called Stem Cells; literally living up to their name – being the stem from which several types of cells branch out. Not just that, these cell types even take up the responsibility of replacing damaged cells in certain body parts of adult organisms. Be it understanding how an entire organism develops from a single cell or exploring its regenerative abilities for treating certain chronic diseases, worldwide research on stem cells has progressed appreciably over the last 40 years.

Prof. Maneesha S. Inamdar’s laboratory at the Molecular Biology and Genetics Unit of JNCASR, carries out fundamental research in stem cell and developmental biology using mouse and Drosophila as the model organisms. One of the long-term ongoing research at her lab is on a gene named ‘Rudhira’ that is fundamental to the formation and functioning of new blood vessels during mouse embryonic stage. The gene Rudhira (meaning blood-red) at first, was found to be expressed in the red blood cell lineage of mouse embryonic stem cells and subsequently has been shown to be conserved between Drosophila, mouse and human! The discovery of this novel gene was quite a turning point since the expressed protein has 98% similarity to a protein from the gene overexpressed in human breast cancer cells (human BCAS3). The later has been shown to have expression even in the embryonic stem cells, most importantly detected to have abnormal expression levels in malignant tumors and blood vessels.

Baseline findings
Further in-depth experiments revealed a vital role of Rudhira in directing movement of cells to particular locations required for the process of wound healing. During development in multicellular organisms, errors during the movement of cells to destined locations often result in serious diseases like formation of tumor or vascular defects. On this axis, Prof. Inamdar’s team established that the gene Rudhira codes for a protein that rearranges and promotes cell division control protein (a protein involved in regulation of cell cycle) during the process of wound healing. Lack of this protein was shown to have severe consequences on cell’s cytoskeletal structure (even though cells are microscopic, they have a skeletal structure too that holds them, aids their movement, plays substantial role in cell division) and orientation that ultimately affect the elemental process through which new blood vessels develop.

Current breakthrough
After establishing and functionally characterizing the role of Rudhira in-vitro, it was then time to replicate the results in-vivo. Ronak Shetty and Divyesh Joshi, two of the current graduate students from Prof. Inamdar’s lab involved in this project, continuing work initiated by former graduate student Dr. Mamta Jain, accomplished in generating the first Rudhira knockout mouse (Knockout literally translates to removal; in genetics it is the process through which an existing gene of interest is inactivated or replaced by an artificial piece of DNA with the aim to study what the gene normally function as).

These images depict normal vascular patterning in the control embryo (left) and irregular and discontinuous vasculature in the Rudhira knockout embryo (right) at day 10.5 of embryonic stage.
These images depict normal vascular patterning in the control embryo (left) and irregular and discontinuous vasculature in the Rudhira knockout embryo (right) at day 10.5 of embryonic stage.

In their recently published paper in Scientific Reports, the team details systematic experiments to show major developmental defects in mouse embryos lacking Rudhira. Rudhira knockout mice embryos were unable to survive beyond 9 days of their embryonic stage and were detected by decline in growth and significantly affected patterning in the dorsal aorta of heart. Through immunostaining and subsequent microscopic structure analysis of relevant tissues, the team was able to show that even if the developmental rate was not affected, severe defects in shape and structure of blood vessels in the head and heart of Rudhira knockout embryos were detected (these embryos had shrunken heart chambers and abrupt dorsal aorta among other structural defects in the development). Expression of this gene was further shown to be crucial for normal structuring and functioning in the inner layers of blood vessels.

Dr. Ronak Shetty (left), Prof. Maneesha S. Inamdar and Divyesh Joshi (right) at Vascular biology Laboratory, MBGU, JNCASR.
Dr. Ronak Shetty (left), Prof. Maneesha S. Inamdar (center) and Divyesh Joshi (right) at Vascular Biology Laboratory, MBGU, JNCASR.

This piece of work led by Prof. Inamdar not only reaffirmed the pivotal role of Rudhira in blood vessel development through in-vitro and in-vivo studies, but has also contributed to the field of developmental biology by establishing a mouse model for future studies in stem cell and medical research in cardiovascular development. For more studies from Vascular Biology Laboratory, click here.

Reference
Shetty, R., Joshi, D., Jain, M., Vasudevan, M., Paul, J.C., Bhat, G., Banerjee, P., Abe, T., Kiyonari, H., VijayRaghavan, K. and Inamdar, M.S., 2018. Rudhira/BCAS3 is essential for mouse development and cardiovascular patterning. Scientific reports, 8(1), p.5632.

The article is authored by Manaswini Sarangi, Evolutionary Biology Laboratory, EIBU, JNCASR.

Cover Art by: Manaswini Sarangi.

Ever wondered what keeps one awake when the sun shines!

blog-3_bnl_cover-sketchFruit flies shed light on neurons driving wakefulness during daytime

Like us, some organisms, are active during the day, while some are active at night and some others are active during twilight. It is believed that such patterns are driven by adaptive forces such as the availability of survival resources like food and mates. Be it nocturnal or diurnal, what controls waking up and going to sleep in the living world? The answer is a daily CLOCK! Yes, an organism’s biological clock wakes it up and puts it to sleep by appropriately timing its activities. Scientists have been trying to understand the mechanisms behind sleep and wakefulness behavior and its regulation by the circadian clock.

Sleep is an intriguing phenomenon that has been observed across a variety of species studied, from mammals to insects (1, 2). “About two decades ago, fly researchers woke up to the potential of harnessing the potential of fly genetics to unravel the mysteries of sleep and its underlying cellular and genetic basis. Since then, mutations on several genes have been shown to impact sleep levels, and several distinct brain regions whose electrical activity either induce or reduce sleep have been identified”, says Prof. Sheeba Vasu, an expert in Neurogenetics leading her laboratory at Neuroscience Unit, JNCASR. While human and fly brains are dramatically different in structure and complexity, the states of being awake or sleep share a fair degree of commonality. These parallels between sleep in flies and mammals (3) make fruit flies an excellent choice to study this behavior.

In a report published in August 2018 in eNeuro (4), Prof. Sheeba Vasu and her student Dr. Sheetal Potdar from Neuroscience Unit at JNCASR, showed that a group of dopaminergic neurons under the action of a particular type of neuropeptide called Pigment Dispersing Factor (PDF) keeps the flies awake and active during the daytime. [Quick Fact: Dopaminergic neurons are the brain cells that synthesize a chemical called dopamine. Dopamine serves as a chemical messenger between neurons that is known to promote wakefulness.] “The main motivation behind this study was as part of a bigger question – of whether the two limbs of sleep regulation, sleep homeostat and circadian clocks communicate with each other to regulate sleep and wake”, says Sheetal, lead author of the paper.

Although it is well known that light and dopamine stimulates alertness/wakefulness let us see how the biological clock talks to the neurons to keep the fly awake. In response to the action of light and dopamine, one subset of the Drosophila clock neurons releases a neuropeptide called Pigment Dispersing Factor (PDF). This neuropeptide is expressed only by some specialized clock cells in the fly brain, and is known to have primary functions driving behaviors related to morning and evening times of a given day. The protein PDF has several target spots in the brain depending on the action required, to which Sheetal adds, Since 2008, we know that PDF also functions in promoting wakefulness. So here was a nice opportunity for us to examine if any of the known sleep homeostatic structures responded to signals from the receptor of PDF, in order to tie in with our bigger question of sleep homeostat-circadian clock communication”. [Quick fact: This neuropeptide PDF with similarities to a crustacean hormone was first described by Dick Nassel in 1993 and the gene pdf encoding it was cloned in the laboratory of Nobel Laureate Jeffery Hall, a geneticist and chronobiologist!]

First, Sheetal established that flies carrying dysfunctional receptors for PDF (called PDFR, pdfr being the receptor gene), were unable to remain awake as much as their controls, i.e. these mutant flies slept much more during the day. Second, by manipulating the expression levels of this receptor gene through fly neurogenetic techniques, she conducted an exhaustive screen searching for the cells that are acted upon by the neuropeptide PDF to keep flies awake. Out of the several strains examined, she found a group of dopaminergic neurons that resulted in substantial increase of sleep during the daytime when the receptor gene’s expression levels were turned down and a significant decrease in sleep when this gene was overexpressed in them. When asked about specific challenges during the experiments, Sheetal said, “Absolute levels of sleep vary to a large degree both across flies and assays; trends that you see in one experiment mysteriously disappear in the next one. This was one of the biggest challenges I faced and the only way to overcome this was to repeat all of my experiments multiple times. Most of the data are from experiments repeated anywhere between 2-5 times to ensure that whatever phenotype we report is a true phenotype”.

This figure represents changes in sleep through out the day when expression levels of pdfr were altered (A) lowered expression resulted in increase in day time and nighttime sleep (red line),(B) overexpression resulted in decrease in daytime and increase in nighttime sleep (purple line), compared to their controls.
This figure represents changes in sleep through out the day when expression levels of pdfr were altered (A) lowered expression resulted in increase in day time and nighttime sleep (red line),(B) overexpression resulted in decrease in daytime and increase in nighttime sleep (purple line), compared to their controls.

 

Further detailed examination in the target subsets of the dopaminergic neurons revealed that even though the daytime sleep was significantly enhanced during lowered expression of the receptor gene and significantly reduced during its overexpression, the nighttime sleep remained much higher than their respective controls. Additionally, it was also shown that once lights were turned on during the experiments, the flies which had overexpression of the receptor gene took much longer to fall asleep than their counterparts. The finding was strengthened when they found synaptic connections between the dopaminergic neurons and the PDF-expressing neurons. Further investigations revealed a subtype of neurons (PPM3) that showed significant decrease in intracellular calcium levels under the action of signals from the PDF receptor, particularly during the daytime.

Can you say a little about PPM3/ dopaminergic neurons in general in perspective of sleep research? Was there a ‘eureka’ moment during your experiments? “Previously, the role of dopamine has been reported in promoting wakefulness. Yet, the PPM3 subset that we think at work here could be promoting sleep. So this is a major finding in the sense that it shows that perhaps the broad set of dopamine neurons consist of distinct sleep-promoting and wake-promoting subsets. Furthermore, when I began using the dopamine drivers, I had no a priori reason to believe that it will respond to PDFR signalling. In fact, there was no scientific thought in doing this experiment – it was strictly a serendipitous finding, and I just got lucky! Moreover, at that time in my screen, none of the other drivers had yielded interesting or consistent results, so more than a ‘Eureka!’ moment, it was a ‘thank goodness!’ moment for me!” answers Sheetal.

Fascinating enough, that even though most known dopaminergic neurons are known to improve wakefulness, these researchers at JNCASR were able to show that there are some sub-groups of these neurons that in fact promote sleep!

What is the bigger question of sleep/wake research that you would like to address at some point? “The most mysterious aspect about sleep is what purpose it serves. Realistically, it is possible to address this question. If I am permitted to be more ambitious, I would like to understand why dreams occur – are they a by-product of what happens during sleep or do they serve a specific function?” says, Sheetal.

So, there we go, for remaining awake the circadian neurons send instructions through the neuropeptide PDF receptor to a subgroup of dopaminergic neurons, that otherwise would be promoting sleep. This noteworthy finding is expected to advance our understanding on sleep/wake behavior. For more studies from Prof. Sheeba Vasu’s Behavioral Neurogenetics Laboratory at JNCASR, click here.

References

1. Tobler, Irene. “Phylogeny of sleep regulation.” Principles and Practice of Sleep Medicine (Fifth Edition). 2011. 112-125.
2. Lesku, John A., et al. “Phylogeny and ontogeny of sleep.” The Neuroscience of Sleep (2009): 61-70.
3. Greenspan, Ralph J., et al. “Sleep and the fruit fly.” Trends in neurosciences 24.3 (2001): 142-145.
4. Potdar, Sheetal, and Vasu Sheeba. “Wakefulness is promoted during daytime by PDFR signalling to dopaminergic neurons in Drosophila melanogaster.” eNeuro (2018): ENEURO-0129.

The article is authored by Manaswini Sarangi, Evolutionary Biology Laboratory, EIBU, JNCASR.

Cover Art by:  Manaswini Sarangi.

Scientists find a novel way for lead-free water

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World’s massive economic growth is undoubtedly the result of the industrial era, which began between 18th-19th century in parts of Europe and North America. With the constant need and greed of human beings, industrialization became colossal in no time and with it we have brought upon ourselves both the positive and negative aspects. Current ecological system has been under perpetual mortification, thanks to the enormous level of pollution in air, water, soil, just name it; owing to the undeniable expansion of mechanisation. Among several other consequences of the above, contamination of drinking water on our planet is one of the most pressing issues of our time. Drinking water constitutes a minuscule fraction of entire water content on earth that renders the survival of a vast majority of living organisms. Release of heavy metal ions like those of lead, mercury and cadmium from industries to water has edged disastrous fallouts in public health. This paucity of clean drinking water has directed scientists over the world to find ways to remove hazardous wastes and purify contaminated water.

blog-2_c Simplistic illustration of ion exchange mechanism for lead capture and removal (in water).

Ekashmi Rathore, a graduate student in Dr. Kanishka Biswas’s Laboratory at NCU, JNCASR, have identified a novel compound for isolating lead from water. Through the traditional process of intercalation – a reversible insertion of a molecule (or ion) into materials with layered structures, Ekashmi synthesised a potassium intercalated layered compound 1 (K-MPS-1, K0.48Mn0.76PS3.H2O ) which is competent enough for efficient extraction of lead ions from water even at extremely low concentration, i.e. 1 ppb which is well below the tolerance level of lead ions in drinking water, <15 ppb as per USA-EPA 2. During intercalation of potassium ion, the interlayer spacing (van der Waals gap) between the sheets increases, creating voids at the manganese sites. In the following step, when the lead contaminated water was allowed to pass through the intercalated compound, the potassium ions were displaced and lead ions got adsorbed into the void sites of manganese, further restoring the increased gap (originally interlayer spacing at 6.45 Å, intercalation increased it to 9.40 Å, then void site occupancy by lead ions decreased it back to ~6.45 Å).

The entire process has been examined in a wide range of pH (2-12) water and works adequately great in being able to remove lead within this whole spectrum. Along with making the compound useable in various types of water content, the team has also shown its high removal capacity (~393 mg/g) of lead ions compared to earlier studies. Further data showed 97% extraction of lead ions in a matter of 4.5h and ≥99% removal within no more than 12h. The course of action being relatively swift ensures its pragmatic nature at an industrial level. They also showed the compound’s precise selectivity in terms of being able to capture and remove only lead ions from a pool of several other mono and divalent ions that are also present in water. Additionally, the compound is stable to oxidisation compared to previously tried methods and hence comes across as an advantage in materialising this reaction.

img_20180407_175937Ekashmi (left) with Dr. Kanishka Biswas (right) at Solid State Chemistry Laboratory in NCU, JNCASR.

In fact, very interestingly, when the same procedure was experimented using water from a nearby lake (Rachenahalli Lake, Bangalore), the compound (K-MPS-1) was successfully able to selectively sequester ~99% of lead ions! So, as we can see, this novel intercalated compound is able to efficiently isolate harmful lead from drinking water through its high removal capacity, its high selectivity, being able to function in a wide pH range, works even when the concentration of lead ion is very low and more importantly being stable.

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Sources of heavy metal and radionuclide in water and schematic representation for the mechanism of lead ion (Pb2+) and cesium ion (Cs+ ) capture by K-MPS-1. (Mn, purple; P, blue; S, yellow; K, black; heavy metal or radionuclide, green).

Ekashmi’s alluring idea accompanied by the prudent experiments led it to a success where her work got published in The Journal of Physical Chemistry (C) 1. She also got an award by The Falling Walls Lab India 2017, following which she beautifully presented her work in Berlin the same year (check out the video). She owes this success to her mentor Dr. Kanishka Biswas for encouraging her to pursue the idea of lead removal despite the main theme of the lab being research on thermoelectric materials. Ekashmi pursued this idea further and implemented it in efficient capture and removal of Cesium, an enduring radioisotope, from water using the same compound K-MPS-1 and similar methodology used for lead isolation 3. Further research on her plate includes mercury removal from contaminated areas and development of prototypes for detection of hazardous wastes in water.

This article is authored by Manaswini Sarangi, Evolutionary Biology Laboratory, EIBU, JNCASR.

References

  1. Rathore, Ekashmi, Provas Pal, and Kanishka Biswas. “Layered Metal Chalcophosphate (K-MPS-1) for Efficient, Selective, and ppb Level Sequestration of Pb from Water.” The Journal of Physical Chemistry C121.14 (2017).
  2. United States Environmental Protection Agency; Drinking Water Requirements for States and Public Water Systems; https://www.epa.gov/dwreginfo/lead-and-copper-rule.
  3. Rathore, Ekashmi, Provas Pal, and Kanishka Biswas. “Reversible and efficient sequestration of Cs from water by layered metal thiophosphate, K0. 48Mn0. 76PS3. H2O.” Chemistry-A European Journal (2017).

Deciphering a new role of a protein complex aiding the Pac-man job inside cells!

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Bagging two Nobel Prizes, first in 1974 1 and then recently in 2016 2, work on Autophagy stands at the cutting edge of both fundamental and application based research. The word autophagy with its Greek origin, meaning ‘self-eating’ (auto: self, phagein: to eat) is one among several efficient mechanisms functioning inside a living organism.

The channel through which intracellular materials such as certain byproducts of metabolism, damaged proteins, those that are brewing for degradation are actively ingested by the cell itself is what defines the course and action of autophagy. These intracellular materials that are intended for ultimate degradation are ingested by a structure called autophagosome or the ‘Pacman’ as aptly called by Dr. Ravi Manjithaya, a research scientist at MBGU, JNCASR. These autophagosomes then play the role of a garbage truck where they transport the ingested cargo into another structure called lysosome. Post fusion with the vacuole (lysosome), multiple enzymes help in the ultimate degradation and absorption of intracellular waste. This process also involves sending back useful items like amino acids back to the cytoplasm.

So, you see there is this whole system of collecting the trash, degrading and eventually re-cycling them! What’s more fun and further interesting is digging out the mechanism underlying the efficient functionality of this integral system of autophagy.

rm-2Dr. Ravi Manjithaya with his graduate student Gaurav Barve at the           Autophagy Lab

Dr. Ravi Manjithaya’s (RM) group at MBGU studies autophagy and related elemental processes using yeast, human cells and mouse as model systems. The molecular components of autophagy were first laid out in the yeast Saccharomyces cerevisiae. His group explores through multiple approaches like, the ‘cargo approach’ to identify regulatory mechanisms fundamental to autophagy by examining which of the toughest cargos can be tackled by this process. For this, his group employs both, a ‘chemical biology approach’ and the ‘classical genetics approach’.

One of his group’s latest works has carried out an unbiased screen for autophagy defects in yeast Saccharomyces cerevisiae, and shown the significance of a group of proteins called ‘Septins’ during the early stages of autophagy 3. Septins, first discovered in yeast S. cerevisiae are a group of proteins that are highly conserved in eukaryotes (although absent in plants) and serve as one of the key cytoskeletal elements in cell division process. Functional role of septins in yeast autophagy was unclear before this study. However, septins have been shown to have role in dynamics of cell membrane shapes. In order to determine the importance of septins in autophagy and their potential contribution to the formation of the autophagosomal membrane structure per se, RM’S group carried out well-thought out targeted experiments using budding yeast cells.

By following degradation of cargo (peroxisomes) for autophagic capture and degradation, RM’s group identified several septins whose functional forms were required in this process. To understand their roles better, the lead author and graduate student, Gaurav resorted to fluorescent live cell microscopy. By following these fluorescently tagged (GFP: Green Fluorescent Protein) septins, Gaurav observed the transition of these septins towards the locations inside the cell that are important for autophagosome formation. Interestingly, the septin-GFP proteins were often found in the shape of ring (roughly the size of autophagosomes) surrounding the pre-autophagosomal structures (PAS), which is the birthplace of autophagosomes. The team further went ahead to examine if the septins had physical interaction with autophagy proteins and identified two autophagy proteins, Atg8 and Atg9 as septin interacting partners. Gaurav elucidated how precisely this septin movement is vital  for providing membrane from various cellular locations for building autophagosomes.

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Overall, RM’s team for the first time exemplified the key role of these groups of proteins called septins in autophagosome maturation, direct physical interaction with autophagosomal membrane proteins (Atg8, Atg9), movement of septins from one location to another and most intriguingly development of septin rings that are similar in dimension to that of the autophagosomes. This study has opened up new questions such as how exactly septins help in autophagosome formation? Since septins interacted with Atg9 vesicles, how do the aid in providing membrane source for autophagosome formation? Does the complex of septins involved in cell division is the same complex that helps in autophagosome formation or are there some additional factors involved in it? And finally, what drives septins off from their usual localization at the bud-neck (region between mother and daughter yeast cell) to the site of autophagosome formation?

This work published in the Journal of Cell Science (JCS), 2018 details the beauty of this entire mechanism at play.

This article is authored by Manaswini Sarangi, Evolutionary Biology Laboratory, EIBU, JNCASR.

References

  1. “Physiology or Medicine 1974 – Press Release”. org.Nobel Media AB (2014). http://www.nobelprize.org/nobel_prizes/medicine/laureates/1974/press.html
  1. “The 2016 Nobel Prize in Physiology or Medicine – Press Release”. org.Nobel Media AB (2014). http://www.nobelprize.org/nobel_prizes/medicine/laureates/2016/press.html
  1. Barve, Gaurav, et al. “Septins are involved at the early stages of macroautophagy in S. cerevisiae.” J Cell Sci(2018): jcs-209098.
  1. Barve, Gaurav. “First person–Gaurav Barve.” (2018).

 

 

Fungal pathogen loses “jumping genes” to gain stability and virulence

In the disease world of fungal pathogens, Cryptococcus neoformans is known to cause havoc among the immunocompromised individuals. Recently another sister fungal pathogen Cryptococcus deuterogattii has sickened hundreds of otherwise healthy people. Researchers around the world proposed that loss or gain of a whole bunch of genes could have been the key behind acquired virulence attributes. In a recent paper published in PNAS, Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR), Bangalore, India in collaboration with Duke University established a link between the loss of RNA interference ((RNAi) genes, reduction in the centromere length and gaining virulence attributes in Cryptococcus deuterogattii.

Sitting at the waistline of chromosomes, the centromere is an essential stretch of DNA that is required for accurate chromosome segregation, and to maintain genome stability. The researchers at JNCASR have been working on understanding the evolution of centromeres in human fungal pathogens for over a decade. In the current study published in PNAS, a team led by Prof. Kaustuv Sanyal identified centromeres in three closely related Cryptococcus species, assembled the genome at the chromosome level and scrutinized the centromeres. Remarkably, the team found a correlation between the centromere length and the presence of RNAi genes that are known to play a vital role in regulating genome and their stability. The two RNAi-proficient Cryptococcus species have large and complex centromeres with full-length DNA sequences called retrotransposons. These segments of DNA can jump around to different positions in the genome and cause mutations or increase (or decrease) amount of DNA. On the other hand, the RNAi-deficient Cryptococcus deuterogattii harbours smaller centromeres without full length or inactive retrotransposons. “We believe that shortening of centromeres in Cryptococcus deuterogattii led to its genome shrinkage that provided a replicative advantage in terms of faster growth rate, possibly contributing towards enhanced virulence of this species” said Prof. Sanyal, lead author and Professor at JNCASR.

RNAi is known to suppress transcription at the centromere. One would imagine that due to the loss of RNAi, transposons present at the centromere would have run wild in the genome! “In contrast, we see that they are in essence gone. The model is that the only way to survive the loss of RNAi may have been to get rid of the transposons from the genome or inactivate them so they cannot transpose anymore” says Vikas Yadav, first author of the study. To understand this, the team experimentally recreated the evolution in the lab by growing RNAi- proficient and RNAi-deficient strains for 1000 generations. Upon sequencing the genomes of these strains, it was seen that in the RNAi deficient strains, the retrotransposons at the centromere had undergone recombination causing shortening of centromeres. This is contrary to earlier studies from elsewhere that reported the suppression of recombination at centromere loci. Results of the current study suggest a role of RNAi in the evolution of centromeres. The team aims to extend the study to understand the impact of genomic changes on pathogenesis and virulence.

This work is a result of a long-term collaboration between the team JNCASR, Joseph Heitman’s group at Duke University Medical Center, USA, Christina Cuomo at Broad Institute of MIT & Harvard (USA) and Guus Bakkeren at Summerland Research and Development Centre, BC, Canada.

This research is funded by JNCASR, National Institutes of Health/National Institute of Allergy and Infectious Diseases, USA, and Tata Innovation Fellowship of Department of Biotechnology, Govt of India.

This article is authored by Kripa V. Jalapathy, Technical Research Centre (TRC), JNCASR.

Journal reference:

  1. Vikas Yadav, Sheng Sun, R. Blake Billmyre, Bhagya C. Thimmappa, Terrance Shea, Robert Lintner, Guus Bakkeren, Christina A. Cuomo, Joseph Heitman, Kaustuv Sanyal. RNAi is a critical determinant of centromere evolution in closely related fungi. Proceedings of the National Academy of Science USA. Mar 2018, 201713725; DOI: 1073/pnas.1713725115

Organic Electronics: Sensors with a flexible future

Organic Electronics: Sensors with a flexible future

In the “Internet of things” era, electronics are embedded in objects and transfer data without human intervention.  BP monitoring bands, non-contact cardiac sensors, glucose monitoring medical sensors, driverless cars and electronic wallpaper and gadgets are slowly refining and evolving our lifestyle.  Well, these are probably just a few of the possible future applications that are being enabled by solution processible/printable electronic and opto-electronic materials.

The availability of softer materials such as organics and polymers which respond to light and emit light, accompanied by reasonable electrical transport properties provide us with options in the world dominated silicon electronics. There has been growing need for niche applications where there are requirements for flexible-stretchable-bendable smart sensors and display elements.

With the aim to provide an alternative to the conventional silicon based silicon photo-detector approach, researchers at Jawaharlal Nehru Center for Advanced Scientific Research (JNCASR) have used a light-sensitive organic compound while the read-out electronics have been fabricated on a polymer organic thin-film transistor backplane. By developing an integrated organic electronic component similar to a CMOS pixel fabricated by printing methods for image sensing applications, Prof. K S Narayan’s lab at the Chemistry and Physics of Material Unit (CPMU) department of JNCASR have made strides in combining organic thin-cell transistor backplane with a organic photodiode layer which is printed on polymer substrate. Since the components of the organic circuit are deposited from solution phase, they can be sprayed or coated on flexible or stretchable substrates. In a recent article that was published in Applied Physics Letters, the researchers have shown that the optoelectronic response of the photodiode (with polymer based semiconductors) was large and sufficient to control the field effect transistor consisting of the polymer semiconductor. The highlight of the results is the demonstration of an organic electronics circuit with an efficient light sensing photodiode and a low turn-ON field effect transistor (FET). It was shown that the output characteristics of the FET were dependent on the light-level incident on the photodiode.

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Prof. Narayan says “the possibility of fabricating circuits by simple dispensing methods with response equivalent to elaborate Si based structures which require complex manufacturing requirements is interesting, and the added features of such devices over large-area on non-rigid and flexible substrates provides some exciting applications in life sciences and ambient electronics sensors. We have some novel strategies to further increase the spatial resolution and the sensitivity of the organic pixel element.”

We have developed a method of spraying or coating of the polymer based substrates, and we believe the method will enable distributed sensor arrays over larger areas than that achievable for silicon-based processes. We will be interested in fabricating a large-area prototype and explore the feasibility in real world applications noted Ms. Swati, PhD scholar in Prof. Narayan’s lab. who spearheads this activity.

This article is authored by Kripa V. Jalapathy, Technical Research Center (TRC), JNCASR.

Reference:

  1. Swathi, and K. S. Narayan Image pixel device using integrated organic electronic components Appl. Phys. Lett. 109, 193302 (2016)
  2. Swathi, K.S. Narayan, Solution processed integrated pixel element for an imaging device, Proc. SPIE 9944, Organic Sensors and Bioelectronics IX, 99440T (September 27, 2016)

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