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hello everybody so good [Music] do [Music] good day everyone and thank you for joining us at this 2021 ceremony of tnq's inspiring science awards this is the fifth year of these annual awards for the best paper in the life sciences published from india in the previous year they aim to recognize and reward quality science to inspire scholarship and to encourage students of science to pursue excellence and do significant and creative work the inspiring science awards have steadily gained recognition in the indian science community and the applications we receive are of impressive scope spread and quality this year we received 554 entries from over 240 institutions across 100 cities in india i would like to thank our jury who worked in three panels and spent the last two months assessing these entries to shortlist this year's six excellent finalists each year applications are invited from young scientists who are registered for a phd up to those in the fourth year of their postdoctoral research training for the 2021 award the research paper must have been first published either online or in print between november 1 2019 and september 30 2020. we intend to extend this period to a 12-month one from october 1 of the previous year to september 30 of the current year this this submission should be full-length research papers that have been accepted and published the author must have been affiliated to and the research conducted at a research institution or university based in india papers with co-authors will be considered but the award will be given only to the submitting author all six shortlisted finalists will receive an isa medal a citation and a macbook air the winner will in addition this year receive a cash award of two lakhs this cash award takes a temporary pandemic place of an all expenses paid travel grant to a life science conference of the winner's choice anywhere in the world we hope to reintroduce the travel grant as soon as possible anuranjan anand proposed these awards as an extension of our annual tnq distinguished lectures in the life sciences and as a way for us to engage with the research community through the year he is professor of the molecular biology and genetics unit and associate faculty and chair at the neuroscience unit of the jawaharlal nehru center for advanced scientific research in bangalore professor anand has agreed to announce this year's winner and to discuss the six shortlisted papers with the finalists they are santosh kumar kuncha a senior research associate at ccmb the center of cellular and molecular biology hyderabad richard mishra a postdoctoral fellow at the laboratory of microbiology and microtechnology lausanne the research for her paper was conducted the indian institute of science bangalore arush mohit mittal who is a doctoral student at iit kanpur ritika tiwari a post doctoral fellow at the cancer biology department learner research institute cleveland whose research was done at iit kanpur xiaomi craig a doctoral scholar at the department of biosciences and bioengineering iit bombay congratulations raj kumar varma a senior research fellow at the laboratory of plant microbe interaction at the center of dna's fingerprinting and diagnostics hyderabad congratulations to all six of you may i now invite anuranjan to discuss the work of us finalists with each of them and then announce the winner of the 2021 inspiring science award professor anuranjana thank you maryam warm welcome to everybody attending this ceremony we have come together to felicitate the finalists and announce the winner of isa 2021 i'm told that today's event is being attended by members of the research and academic community many of the institute members from where our finalists come from families and friends of the finalists isa winners of the previous years entrusted members of the public colleagues from the tnq thank you everyone for joining this ceremony on one hand this event is unlike previous years where we are missing out on the distinguished lectures and from the students and finalists point of view the whole excitement of an auditorium experience and thrill of getting to know that you are the one of the finalists or the winner the reasons obvious reasons that everybody knows about it and we also know that from now on things can only get better on the other hand for the isa 2021 this year has been much like the previous years except a bit better for the number of entries received 550 plus as mariam indicated from the number of organizations that participated 240 plus that's hugely encouraging as you know these awards aim to recognize and reward quality science to inspire scholarship and encourage students of life sciences to pursue excellence and carry out creative work and publish that going forward the number of entries mentioned may just continue to increase which is a testimony to the presence of a vibrant research community in biological sciences working on many aspects and flavors of the subject which is something becoming evident in the range of papers which gets submitted in these previous years is what i am told each year applications are received from young science scientists in the country the process of submission is simple i am unsure if it can be made simpler it needs no recommendation no nomination no forward letter one has to simply go forward and uploaders submit what one considers is the best published paper while working in an institute in the country during phd or early stages of post-doctoral training the idea of this award was proposed over five years ago to create a connect between the students and young researchers beyond the tnq distinguished lecture series the award is largely aimed at phd students in the country or young researchers i'm excited about this fact because i get to interact a lot with phd students phd is perhaps the longest jump in the growth process of one scientific journey and whether one realizes it or not at early stages before one reaches a level for example to submit an article for the isa award as this process unfolds it tests one's enthusiasm passion motivation on one hand ability to think logically scientific reason many experimental skills knowledge of several techniques and methods time management skills abilities to organize make presentations collaborate face rejections of papers enjoy acceptance of papers which is sort of a very very exciting time for any scientist and these attributes stay with one and in fact grow no matter what one takes up as a profession subsequently so phd studentship indeed equips no matter what one does subsequently with many high level skills crucial in professional life and by employing these in right manner one can create a win-win situation wherein one almost never fails a life in a larger sense of the world just have a look at the value and the role of a modified pcr technique in these previous months and one gets to learn many more methods during phd or post doctoral training tnq's foundness to connect tnq's desire to connect with the students by way of the lectures and isa is well known but just in case someone is unaware i shall reveal that it took no more than a minute or so for maryam to get convinced about the idea of initiating isa and continuing commitment of the tnq team to nurture it to think of ways to expand its reach in the community of young researchers and students in the country today we have an opportunity to join with the finalists discuss about their work with each one of them in the presence of many eminent members of this scientific community friends and families are off of the finalists and my congratulations to each one of them i request all of you to put your hands together to congratulate all our six finalized before we move on to invite santosh kumar kuncha hello okay so we we warm good evening to all of all right so yes you're very much audible um so let's let's uh i would like to begin this process uh with uh santosh kumar kuncha who is currently a senior research associate at the center for cellular and molecular biology hyderabad santosh what i need to know from you is while you are currently at the ccmb um where did you do your masters in undergraduation so i have done my master's from the ntu hyderabad they are learning technological university whereas my undergraduation from loyola academy always especially in there and when did you join ccmb i joined the ccma in 2014 for phd program and i've recently submitted and defended my wifi in the last term wonderful wonderful yeah so you know we uh you know santosh uh koncha has uh published a very nice paper uh in e-life um i'm not sure how many of uh people have seen your article i'm sure almost all the members attending this function in ceremony today and your paper deals with uh an unexpected result from the genome sequencing projects yeah given that i uh sort of think a lot about the human genome i'm told there are about 300 or so iso decoders in human genome and i'm sure there are many more in animal kingdom yeah um what about plant kingdom these decoders are not in the plant kingdom is is that the yeah no uh even plants have many iso decoders uh but the functional characterizations of the plant thing is still going on so that has to be looked at so it i mean it's just an emerging field with respect to iso decoders it's this term itself we just come to know i mean a few years back this term iso decoders has been introduced and the work is just started to begin so earlier if you look at bacteria it just has around 50 trnas or 40 to 50. if you look at as you're rightly stated humans are around 300 iso decoder but if you look at the numbers also even the numbers it's nearly 600 t are nice and human but plants are no exceptions to this with the increase in the genome size there is an increase in trna numbers also but however the functions of these are just coming up so recently there are many articles which talk about trnf fragments role of trna and many other conditions such as cancer ribosome biogenesis regulation epigenetics so there's much more to it the field is just coming up right so the title of santosh's uh paper is genomic innovation of atd alleviates mistranslation associated with multicellularity in animalia you indicate that trna expansion of decoders is what you mean has led to mis-selection resulting in critical error of alanine mischarged onto trna 3 on e which needs to be proof read by an enzyme called animalia specific trna dsi lays atd you've gone on to show that in addition to atd there's a threonine trna synthetes thr rs which can clear the errors in cellular scenario and then you mentioned about two tyre functional redundancy for the quality translational quality control or surveillance um would you elaborate and then you tie in a very interestingly story of reactive oxygen species etc so how is all this uh put together i have read some of your additional articles on the subject where you mentioned that atd is a paralog of dtd are there more players like atd and thr srs which are likely to be present so i found this sort of very interesting and fascinating area of work and i would like that you elaborate uh in about two minutes time uh a bit more about this before we move on yeah so uh as rightly mentioned uh the title itself tells that you have a new enzyme to take care of a mistranslation which is induced because of oxidative stress if you move from a single cell organism to a multicellular organism the functionality of the cells is the form and hence the raw's production also increases it's not that rough is bad ross is actually used as a signaling molecules in case of multicellularity it's well characterized as a but excess rose is deleterious to the cell but when we identified this protein uh what is uh we came across this increases in uh number of trnas in animalia and if you look at there are few trnas which are charged with alanine which are supposed to be charged by a throne so wrongly selected wrongly here and this will lead a mistranslation at the proteome level so this needs to be corrected just like our dna replication we have uh proofreading domains similarly we have proofreading the enzymes working at different stages we are talking about the translation and this tr we wanted to understand how it works when we initially did a knockout of atd we realized that this cells are happy but the moment we started giving the uh ross from external source then the cell started showing stereotypic effects because of mistranslation so then that struck us the idea there has to be something in the cell which is sensitive to ross and that is where we discovered another enzyme at estrella tr necessity and we realized that even that can edit so earlier reports have never spoken about through nlprns entities editing lln it is always shown to be edit l sharing so it was totally unexpected in their terms but we could show both in vitro and nvivo that 300 are missing the case when it is active it actively desolates lining which is mischarged on tr next room therefore it does not allow creonin to align in miss translation episode so if you look at uh there is a functional redundancy which is so during oxidative stress one of the protein is suppressed basically it's inactive the editing function is an access so you need another protein which takes care of this if you look at the recent advances in trna biology so one of the question which we believe is very very important and not yet addressed how are trna is rooted from translation to non-translation function away from translation so having right so that's really that's really very interesting uh what i'm going to do is have you in jnc at some time point and have all our students listen to you we we need to move on uh thank you so much for sharing this very fascinating work with us and congratulations to you thank you thank you thanks a lot so um now i want to invite a finalist richard mishra richard has published a paper in science translation medicine hi richard how are you hi everyone i'm good how are you very fine thanks um and the title of a paper is targeting redox heterogeneity to counteract drug tolerance in replicating mycobacterium tuberculosis richa mishra has done her phd working in the indian institute of science bangalore before joining iac where were you richa for your masters and undergrad before we move on to asking about your work i did my master's from the department of microbiology at the university of pune and i did my bachelor's in microbiology at saint xaviers college in calcutta which is my hometown okay so richard um you know your paper deals with a sort of very important problem an unusually long term treatment is required to cure tb in humans is one to all of us and this is necessary to prevent relapses due to genetically drug sensitive bacteria that becomes transiently resisted inside the host cells and tissues and you have gone on to examine mechanistic basis of this in in a very uh intriguing way to me you have exploited uh heterogeneity redox heterogeneity uh which seems like a very subtle phenotype biochemical physiological phenotype and have gone on to do a wonderful omics work which has revealed involvement of iron sulfur cluster biogenesis hydrogen sulfide gas drug reflex pumps and antibiotic resistance um would you tell something more about how this idea stuck to you um what was a sort of interesting uh while you were thinking about and developing this question that this is what you want to address because i i felt sort of very excited about just reading the title and after that many aspects of your paper so tv has been a really tricky disease to cure even after 100 years of discovery of the bacterium that causes it and a very important phenomenon to consider for this is multi-drug tolerance where bacteria transiently are able to tolerate high concentrations of different classes of antibiotics uh it's interesting to see that there are reports which show that this happens specifically when the bacterium is residing within its host in macrophages or in other immune cells in the host and this leads to the generation of many different subpopulations within one single bacterial population that infects an individual so what we're essentially looking at is heterogeneity in bacterial fractions within a single host or it within a single immune cell so this work was done uh at the red with the redox biology group where i did my phd under professor ahmed singh's mentorship and this has been a question that the lab has been trying to address for some time now and in this regard the group had developed a biosensor which was specific to the redox state of mycobacterium tuberculosis which is the positive agent of tb now uh it's important to look at the redox state of bacteria because a lot of the stresses that this bacterium faces when it's engulfed by say a macrophage in the human lung are all radical in nature you have low ph you have generation of reactive oxygen and nitrogen species and so all of this have a very direct consequence on how it reprograms its redox metabolism because that does allow it to survive for very long even through therapy even through exposure to different antibiotics so the group has developed this biosensor a redox biosensor that helps us non-invasively quantify the redox state of bacteria in real time while it's within its host cell and what we were trying to understand is how we could use this biosensor to uh probably characterize phenotypic heterogeneity that could lead to multi-drug tolerance and we discovered that once inside the host cell like a macrophage bacteria very rapidly diversify into different fractions some of which are more tolerant to multi-class antibiotic exposure than others and what we wanted to do with this finding was to characterize how these different subpopulations are different from each other what allows one bacterial fraction to be more tolerant simply by readjusting its redox state under certain conditions of stress like host residence or exposure to antibiotics so it's a very subtle phenotype in some sense it's not a very dramatic redox potential differences i was looking at the numbers that you have indicated they sort of differ marginally and that makes so much of difference and has implications on downstream pathways really wonderful are you continuing on the same line of work in lausanne so what i'm doing here is uh since we talked about phenotypic heterogeneity just now and how uh different conditions within the host can lead to the generation of different subpopulations or bacteria that differ from each other even though they are all genetically identical what we are trying to do here is uh try to understand how drug action differs at a single cell level so if you have a population of 100 bacteria we believe that not all bacteria in that 100 genetically identical population would react similarly to antibiotic exposure and we're using microfluidics and time lapse imaging in real time to look at how single cells in a bacterial population can differ in the way they take up react to and take care of antibiotic stresses during infection that's wonderful thank you thank you thank you richard and congratulations to you thank you okay let's move on uh to invite um ayush mohit methu uh you are working in department of biological sciences and bio engineering indian institute of technology kanpur in within gupta's lab and you published a paper in nature communications multi-network properties overcome random connectivity to enable stereotypic sensory responses yeah very very nice piece of work uh if i have to reflect on this a bit what i know is that stereotypic behaviors they sort of have evolutionary advantage uh i have studied them in context of courtship uh sexual uh activities etc in insects and they can increase fitness uh and speed um and in that context uh fixed action pattern of neurons is thought to be produced by a hardwired neural network in response to uh stimulus uh neurons in some areas show random connections and in other area areas fix connections and you seem to propose that can the brain regions which receive inputs from non-stereotypic connections can generate studio typical responses that's something very intriguing so um how does it happen i mean you say is your red same as my red or is your fragrance same as my fragrance whichever one would you tell us a bit about uh how did you go about raising this question addressing this question you're working on a phase of locus and flies and in particular tell us a bit about what is pred the new matrix you have evolved and how it is better than others um you have about two minutes to tell us about your exciting one yeah it's a lot to tell but so yeah so the basic question we started with was uh when we looked at the insect all practices which is the system that is involved in finding different orders so within that in drosophila and locus and even in other insects there is a multi-layered system of neurons that is present there and it was and in drosophila light is known that there are there is one layer of neuron that connects randomly to the next layer of neurons so by that we mean that if we have two individuals of the same species they will have very different connections but just after the second layer of neurons is another layer and the its responses are measured in locus and they are found to be very similar in different individuals so that form the base of our hypothesis that how did random connections lead to very similar responses and we went about it by using uh simulations and a mathematical analysis of the circuit so we created the circuit in within using code and also using mathematical principles and we found that it is based so the the the layer that receives random corrections so it preserves the information about the different orders within the layer itself so the entire population itself the entire population of cells comes together to store the information and that is how they can preserve the order information within the next layer so that is one of the results and there are other properties like the non-linearity of the the input that the layer receives and so neurons are non-linear in their behavior so whatever input you see using different kinds of connections so they do not do a direct linear transformation of that so based on that those are some of the properties that help the neurons to preserve this information and pass it on to the next layer and the second part is about spread so thread is a metric that we want to capture the stereotyping in the system so generally people use correlation so correlation between two different vectors is true and correlation by itself mostly captures how the two different vectors behave so if one vector is increasing and the other vector is also increasing in the same way then the correlation will be positive if the other vector is not increasing then the correlation will be zero it could be negative also right but it does not really capture the absolute values of so of the response so let's say we have uh so by absolute values i mean that whatever is the spiking response of a neuron that is the absolute value it can capture right so correlation uh kind of ignores that so if we have two vectors like 1 2 is one vector and 2 4 is the other vector then the correlation will be 1 and for one two and three six also the correlation will still be one right so it cannot really capture that the change in that absolute value of the second vector but yes i mean i i could appreciate the strength of your method as compared to the previous methods and has come out very well in your writing so many congratulations to you irish a wonderful job thank you very much for joining in and all the best um we need to move on uh i would like to invite uh sean mcrae uh charming would you please uh join us uh shawnick has published where are you shaming charming has published a paper in nature chemistry alphasyn nuclear aggregation nucleates through liquid liquid phase separation uh wonderful piece of work uh involving uh 22 authors from four departments and organizations right which in itself uh is terrific so congratulations thank you for participating uh uh in this large collaboration and making uh things happen um you know my perspective of uh alpha synuclein uh is from a very genetic point of view as as uh you would know that this gene um was found in kindred from conscious army in italy uh in early 90s this work began and i think around 97 or 8 the gene was found and discovery of this gene was a very powerful story in human disease gene identification to the level that this discovery was mentioned by president clinton in his 1998 state of union address it was a pre-genome era chromosome 4 had another important gene of huntington which was found by the work of several scientists working from 84 to 93 and then about nine years after that the gene force parkinson's came in now it's a story which is continued for almost 25 years or so and you have added a very unique biochemical biophysical angle bringing in liquid liquid phase separation to address early events of the aggregate formation and you have used wonderful techniques in vitro experiments cell biology bringing in mutations all put together in one paper would you have tell us in about two minutes uh and just disentangle this for us to some extent sure sir so uh we know that sydney clean aggregates and form amyloid fibrils which is the higher order structures of this protein is very toxic to the cells which leads to neuronal cell death but we didn't know that what triggers or what initiates the process of this aggregation how in a cell or in a test tube these centipede molecules can come together to form higher order structures so this is what we exactly uh show in the paper that liquid liquid mixing or liquid phase separation can be one of the initial events that brings all of these synoptic molecules together in a very tight space and in that membrane-less tight compartment which is a droplet essentially the concentration of the silicone molecules reaches to that extent so that it can nucleate the aggregation process and we see that exactly that is what happens in euclidean can form aggregates inside these droplets and very interestingly um the factors that promote the aggregation of syndicate are pde uh you know parkinson's disease symptoms in general they kind of also accelerates the process of phase separation of significant as well and dopamine as we all know that dopamine is used as a therapy against parkinsonism right that has shown to be inhibiting the phase separation process as well so there's a direct correlation between the liquid liquid phase separation and alpha cylindrical aggregation that is what we exactly find out and also in detail we we show that at a single droplet resolution from inside the droplet we have taken the isotropium and the rigidity of the molecules and we have done frap experiments to show that the translational as well as the rotational dynamics of these molecules inside these droplets slowly become slower and slower because they are aggregating inside so they are becoming more and more restricted and also we've seen uh show in real time that uh how the fibrils are actually present inside these droplets uh by various techniques and we have used as as you mentioned that we have used mutations in the mutations that has since the process of aggregation also has some space separation and otherwise nuclear ifc nucleon has propensity to form aggregates yes why it does not happen in the wild type or a normal situation as well or does it happen but it's not harmful several yes there are several hypothesis uh one of the very popular hypothesis is you will get parkinson's if you live for 100 years as will eventually aggregate but just that the time is different for different individuals but another hypothesis is yes the endogenous expressed nuclear levels are so low that they cannot form nucleus until there is a little drop stress so there is something wrong with the cells already so there has to be a predisposition there has to be some reports suggested that there can be metal toxicity which can act as a predisposition behind packet system that leads to that is exactly we show in our paper as well that copper and ferric ions right these transient metal ions they induce loss in turn that ross kind of makes these condensates formation inside kila celsius yes thanks i read your paper in great interest congratulations uh thanks for joining uh let's move on uh to invite uh ritika tiwari hello sir hello all the finalists yes congratulations you have published a paper in nature communications androgen deprivation upregulates pink one expression and potentiates cellular plasticity in prostate cancer now um i see that you have sort of tried to sort out a genetic regulatory conundrum involving spink1 res of a special type of prostate cancer all right now i'm aware of the fact that prostate cancer is caused by one of these very curious temporary erg fusion and a large number of patients are due to that chromosomal i think translocation event et cetera et cetera um so um where do the kind of patients you are looking at fit in uh and how did you uh come up um with this gene regulatory cascade and interplay of that and what is this value in context of the treatment so uh if i talk about the tm process to work gene fusion it is the most recurrent gene fusion in when we uh talk in software prostate cancer and it is like present in like 50 to 60 percent of the prostate cancer patients yeah so how are there are other subtypes like the second most uh lethal subtype that would be called as a springbone over expression which is a serine protease inhibitor causal type one protein which is like over expressed in 10 to 25 percent of the prostate cancer patients and it is associated very adverse symptoms like early biochemical occurrence or increased metastasis etc so uh we all uh we are all aware that ar that is androgen receptor is primarily the governing factor or the driving factor for team presses to erg fusion and uh it has also been it was also been established in the literature that the impresses to org fusion is actually mutually exclusive to spank one over expression subtype so the question it came us came to us naturally that if ar is actually driving team to a fusion and pink one is mutually exclu over expression is mutually exclusive to temperature storage fusion then what is the status of ar uh uh ar signaling and what is the state correlation of androgen receptor signaling in context of pink one over expression and this kind of let the whole uh like the whole story like unfolded it uh uh in front of us then we'll uh and since uh androgen persons ar is the common driving factor into impressive to org fusion and many other prostate cancer subtypes what happens is that adt that is androgen deprivation therapy is kind is uh sort of used for the treatment however we found out that ar that is like a in uh androgen receptor actually negatively drives by a pink one expression and uh we found out that if we are giving ad like androgen deprivation therapy to the patients which are actually sprinkling positive in nature what would happen is uh actually it will elevate that repression that pink one had and leading to over expression of further increased expression of pink one and this uh increased expression of pink one actually promotes cancer progression rather than actually suppressing it so the conventional therapy which is good for uh which might serve the purpose in other subtypes might not hold true for uh in context of spring point positive uh prostate cancer cases and another thing that that uh and uh the other thing that we identified was that uh ar along with its core repressor rest actually are uh you know diving this process of repression and further we i also identified that if we if the patients are uh patients are given adt it leads to the development of a lethal subtypes neuroendocrine prostate cancer and we found out that through patient studies as well as through cell lines and publicly available uh oh mixed data we will able to identify that is pink one actually correlates with these this neuroendocrine phenotype which is in fact very difficult to treat and no therapy as such for that and uh to uh to conclude our study we were able to uh uh identify one of the uh one of the small molecular inhibitors against even protein which actually stabilizes the rest protein and that might be used as a you know therapy and as an alternate therapy uh for springbone positive uh prostate cancer patients instead of conventional adt but you have you participated in a large collaborative project almost 15 authors many institutions it's a really privilege it's really privileged to get involved in such work because many of the future studies in biomedical areas the kind of thing perhaps you like are going to be of that nature wonderful training wonderful piece of work many congratulations thank you so much thank you thanks um let us move on to invite raj kumar verma is a student at center for dna fingerprinting and diagnostics raj where were you before joining cdfd uh i did my master's in this food institute okay and i came here you're under graduation in assam too and no no i am from rajasthan so i did my undergraduation over there and vs college corporate leads near the airport interesting so i think education lets us travel and see a lot of interesting places now um you know you have published a paper in cell reports uh a bacterial phytochrome mediates interplay between light sensing and the second messenger cyclic gi gmp to control social behavior and virulence you indicate that light is one of the most important environmental signals and is sensed by diverse forms but many attributes of this aren't very well understood and you reflect that bacteriophytochromes are the most abundant and ubiquitous lyse sensing receptors in bacteria that are involved in time of the day behavior or responses that's very versatile power their biological and regulatory role in non-photosynthetic bacteria is poorly understood and less is known about how they regulate diverse cellular processes you go on to study hph very interesting abbreviation xentomonas origin bacteriophytochrome from this plant pathogen which causes bacterial leaf blight of rice and perhaps of other bloods as you indicated now uh would you tell us you've carried out elaborate piece of work but we want you to give us a sort of slice or a flavor of that telling us about virulence program that is uh regulated molecular how it is associated with the functions and you have carried out a genome-wide expression analysis of uh sobp hp regulon and reached very specific answers uh from that kind of ohmic study which isn't easy actually so we want to hear from you something about this work so this in general bacteriophytochromes are having two modules one is sensory module which is made of pass gap and phi domain and the other one is response regulator which is in general in phytochromes registered in kinase but this phytochrome from the xo doesn't have that response regulator instead it is having past domain which is in general involved in the sensory things so this makes it it's interesting so what is the downstream signaling for this bacteria after life sensing so we started looking at its protein structure because that is the only thing which can give us hint about the functionality of the protein so we then we found that gap domains from the literature that gap domains are all involved in the cyclic nmp or the nfp levels of cellular modulation which in turns binds to different response regulator and function according to the signal they receive so in that case we started looking uh what kind of nlpg it can modulate so we we have done the uh non-specific substrate using uh peripheral phosphor you know this bpp uh and we have done the pda uh phosphodiesterase activities and we got a signal that it's actually having a possibility activity then we started looking which one is the specific substrate for it so we have tried with different uh these nucleotides and we got that it say cyclic dye gmp specific phosphodiesters then we started looking okay it's it's sensing the light signal and it is having phosphodiesterase activity what is the physiological relevance for the bacteria uh after sensing the light how it is helping the bacteria in its physiological activities so this bacteria naturally enters in its host by uh hydrothorpes which are agile openings okay so bacteria is always on the epiphyte on the phyllosphere it has to find these hydrators and it has to enter so for that it needs some signal so in that we we have proved from our paper that in in its natural mode of enter it it takes the signal and it modulates the cyclic digest level in in in turns those levels will change the wavelengths associated functions and they will they will guide the bacteria or the timing of bacteria to enter into the host so this is what we have overall revealed from our work thank you raj uh congratulations to you the team and the lab um really enjoyed your coming here and sharing your work yes many congratulations we need to move on uh to the next step in the process and that has to do with announcement of the winner you know in spite of rather close competition uh one of the papers of one of you stood apart according to all the jury members [Music] that work is to divorce at the level it has been done um and that individual has gone after an important problem in a very bold manner attempting to address key questions about biochemical physiological and molecular attributes of the process a number of different experiments masterfully executed starting with confocal and flow cytometry categorize the microphages on the basis of subtle redox potential phenotypes and going on to address the key attributes to molecular level um which reflect on mycobacterium capacity to tolerate the drugs i think is no secret in the manner i have gone to describe our winner uh is richa mishra let's congratulate uh richard mishra on this achievement uh it's a major achievement uh going by the fact that we had 540 plus entries um six of you are all winners in some sense because it's a very very small percentage and it's been challenged for nearly 30 plus jury members to select six finalists from across the regions uh but richard mishra's work stands out so very many congratulations uh to you uh richa and i'll stop here and hand over the process to the tnq members [Music] see richard's work uh has established a link between phagosomal ph redox metabolism and drug tolerance in replicating mtb and suggested repositioning of chloroquine to shorten tb therapy and achieve a relapse free cure richard hello hello sorry um anuranjan i'm delighted to welcome dr samia swaminathan our surprise special guest of the ceremony dr swaminathan as you will all know as chief scientist the world health organization at geneva and a widely cited expert on various aspects of covet 19. samia swaminathan is a clinician and a pediatrician by training and a globally recognized research on tuberculosis and hiv she spent most of her career as a researcher and then as director of what was earlier known as a tuberculosis research center in chennai trc it is now called the national institute for research and tuberculosis before dr swaminathan moved to the wwho in 2017 she was dieter general of the icmr and secretary to the government of india a highlight of her leadership at icmr was bringing scientific evidence to the formulation of health policy and the development of research capacity in medical schools in india samia swaminathan has published more than 350 peer-reviewed articles and book chapters she's an elected foreign fellow of the u.s national academy of medicine and a fellow of all three science academies in india it is act and an honor the dr swam samya swaminathan has agreed to interact with our 2021 inspiring science winner richard mishra and to discuss her paper targeting redox heterogeneity to counteract drug tolerance and replicating mycobacterium tuberculosis thank you dr swaminathan for being with us today may i now invite our winner richard mishra back to join a discussion with you dr samir samyan swaminathan joined by richard mishra thank you maryam and first of all congratulations richa thank you mom i understand that you are also in switzerland in lausanne up the lake and hopefully pursuing your your work on tuberculosis i'd also like to congratulate all the others who were shortlisted and who were interacting earlier in the program today and it's clear that you know to be six out of 500 young scientists selected as a finalist is is wonderful so congratulations to everyone and this and thank you for your work and hope that you will keep up with your own areas of interest that have brought you to this point um i think tubercles is very close to my heart of course um because i have seen the impact that tb has on individuals on families and particularly on children who often get the most severe forms of tb like tb meningitis and malaria and disseminated tb and despite all of the advances over the last decades in better diagnostics and better treatments which took a long long time to develop we still you know face more than 10 million new cases and over one and a half million deaths a year so we see today with kovitt that every death is tracked every death causes moral outrage and the world wants to come together to solve the problem we've been able to develop vaccines within a year and there are hundreds of trials going on around the world to develop new drugs and new vaccines for for the sarco v2 virus but that level of interest and funding and attention has not unfortunately tb has not had that maybe because it's an ancient disease it's been with humankind for a very long time and people just accept the fact and i think also an important fact that it does affect the developing countries or the lower middle income and low income countries and even within countries like india it's clearly the poorer sections of society who bear a disproportionate burden of tb even though it's an infectious disease so theoretically infects everyone or anyone but the risk factors and the determinants uh the social and economic and environmental determinants are unbalanced so they they're born much more by the poor now coming to the paper richard i'll ask you to to say more about that because it's a very interesting exploration that you have done and on this concept of drug tolerance and mycobacterium tuberculosis which is uh relatively recent and there's been so much work done including by a good friend of mine dr lalitha ramakrishnan who using the um the the the fish yes the zebrafish thank you model you know has really gone in depth into the structure of a granuloma from the early stages of how granuloma forms and has gone into a lot of the molecular mechanisms of happening within those granulomas and that molecular understanding is important because that's how you can then start thinking about how to target drugs at each of those different levels of different enzymatic pathways that get involved now drug tolerance is an important as you point out in your paper mechanism for survival both of actively replicating and non-replicating mycobacterium and i think anything we can do to make the current regimens more effective um current regiments last from six months to 24 months and that's far too long it's expensive it's toxic it's inconvenient and therefore you know the so-called host directed therapies which act through pathways within the uh the human cells uh in this case a macrophages uh in a way that they facilitate the killing of mycobacteria as an important area to explore so there have been many drugs that have been postulated to have an impact on drug tolerance and i think the evidence you provide for chloroquine needs further exploration definitely i think the animal models seem to be promising but we need to then take this work further and see whether it can go into the clinic and that's where we need the linkage between the basic scientists and the uh the clinical researchers i think that i'm not sure what you're doing at epfl you can tell us but there's obviously a strong group there that works on tv as well and um so wish you all the best again congratulations and i hand it over you to you now to see a little bit about your work thank you very much um so as dr swaminathan described tb has been around for a very long time and an absolute effective relapse free cure still remains elusive for us so i think the inspiration behind the paper as dr swaminathan mentioned was when professor ramakrishnan showed how residents within the host can induce drug tolerance and not just in non-replicating bacteria but actively replicating mycobacterium which is which was digressing from the the the general dogma that that was in the field that only non-replicating bacteria can tolerate antibiotics because of a general shutdown of metabolic and physiological mechanisms so uh that inspiring piece of work uh was very important for us to define our questions to understand how actively replicating bacteria can diversify within the host to tolerate antibiotics and i think it was not only important to discover or to to look at these bacteria in these in these models but also to identify what host cues are crucial to the generation of these these uh drug tolerant bacteria uh we were able to do so uh we were able to define ph acidification in the phagosomes to be an early christian cue that leads to the generation of drug tolerant bacteria some drug tolerant bacteria inside macrophages and uh the most important part of the paper i think is is the fact that we can use chloroquine which is an already approved safe drug already be already being used for the treatment of malaria in the field uh to to be used as a host directed molecule that can sort of homogenize these different subpopulations inside the host to make them uh definitely more susceptible than they normally are to the multi-drug treatment that tb patients receive because they're already given a combination of four antibiotics for six to nine months in the simplest cases so uh if addition of cq to this combination can make a more efficacious regimen to not only reduce the bacterial burden within the hosts but also to prevent any relapse or to generally shorten the duration and prevent the appearance of drug resistant strains of tb i think that could be a very important point to look into in the future to just make tb management more effective and and relapse free thank you richard i'm sure you are aware of the department you graduated from has a long history of contributing to the basic research in the area of tv with dr t ramakrishnan former professor and chair so at various time points various levels that department has played a sort of significant role in this research so congratulations [Music] as we come to the close of inspiring science awards 2021 ceremony may i thank dr swamiya swaminathan the chief scientist of the world health organization in geneva for taking time from her very busy schedule to grace this occasion with her presence and for an illuminating discussion with dr richard mishra very many thanks to you dr swami swaminathan for joining us thank you thank you entirely my pleasure and i would have loved to listen to all the other discussions as well that you had with the finalists but uh yeah it was a really matter of time but thank you so much for inviting me to share with richa and to congratulate her and i hope that this work can actually progress very often we see excellent work done by basic scientists but that remains as a very good paper and doesn't progress and we really need that translational part of research to to become much stronger i think not only in india but around the world and we've been talking here about new models of drug development where we don't wait for big pharma you know to come in and pick up but we really have a public private partnership with the government with academic agencies and labs and the private sector and this is something that we should promote in india because i think we have all the different components it's a question of bringing them together to really focus on our own priorities and and to try to bring science and and link it to public health thank you so much okay so uh my warmest congratulations to everybody to richard sharma wish you many more greater peaks of achievements in your career and i stop here thank you richard would you like to say a few words um thank you uh i'd like to share this with all the finalists where we are at i'd like to uh thank the jury and uh tnt technologies for uh choosing our paper for this uh honor uh to uh everyone who's worked on the paper all my collaborators and colleagues everyone at isc it was a great place to do your phd uh but most importantly to my phd mentor uh professor amit singh who is like a constant source of inspiration in my career and i probably wouldn't have done any of this without his support and guidance and uh to my friends and family thank you very much thanks richard and throw a party for your house i've been isc and in las vegas all right so um as we uh come close to the uh inspiring time forwards 2021 ceremony i would again want to thank dr samya swaminathan uh who took time from her busy schedule to grace this occasion with her presence and thank you professor anuranjanan you are the architect of these awards for being our chief guest and announcing the winner and also thank you for the illuminating discussion you had with each one of our finalists um i also would like to thank all of the 32 judges panel chairs and jury members who took time to evaluate these papers despite all their academic and research commitment 500 for 550 odd papers um applicants application for the 2022 inspiring science awards will open on october 1st this year i expect we will receive even more applications this year and we are starting to plan for that um i want to mention uh and thank two of our previous winners for joining us today they are the inspiring signs of dinner for 2020 subhash mehto and the winner for 2018 uh nishan chetigar um a special mention to everyone at tnq who worked very hard to make isa 2021 possible uh kuri shankar praveen shri ganesh swapnil kitana sam vindhan thank you guys on account of cobit 19 related travel and other restrictions this award function has had to be online and could not be part of the 11th edition of our tnq distinguished lectures in life sciences professor jennifer doudna of the university of california berkeley was scheduled to be our featured speaker this year as most of you know uh she helped pioneer the study and use of crispr cas9 as a tool for gene editing and was awarded the 2020 nobel prize in chemistry along with uh professor emmanuel charpentier how much of what awaited a set of lectures has now been rescheduled and professor doudna will uh we expect present her lecture in bangalore mumbai and delhi in january 2022 today's event has been attended by close to 300 members of the research and academic community many from the institutes that our finalist represents family and friends of our finalists interested members of the public and my colleagues from tnq thank you everyone for joining the ceremony and congratulations once again to all of our finalists and the winner richard mishra i wish all of you great success in your scientific research career all the best stay safe and stay well thank you for joining [Music] you