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  • Okay.

  • Uh, good morning, everyone.

  • Welcome to Icer and kudos to the team for putting this event together.

  • Let me get straight to it.

  • I am a biologist by profession, and that's what I'm going to talk to you about today.

  • But before I start talking to you about biology, let me confess that biologists love labels.

  • We love complicated names.

  • We come up with all sorts of complicated terms to describe best little sub discipline of biology that be all study.

  • But biologists, essentially irrespective of what label he or she is hiding behind, is essentially interested in studying one thing right trying to understand life.

  • We all want to know what it means for foreign organism to be living.

  • What allows this organism to continue to live, what life used to be like in the past, what it's like today and what it's likely to be in the future.

  • And like all fundamental things, life is incredibly hard to define, But it's very easy to describe, And so that's the route that we typically take.

  • We like to describe life.

  • We like to understand it by looking at its properties on one of the most ironically unchanging properties of life is its ability to keep changing right.

  • So what life does all the time is exist in a state of dynamism, constant flux.

  • Everything is always changing.

  • And what's amazing about these changes is that they're occurring at all levels of organization, right?

  • So they're occurring at the level of proteins moving around inside the cells of your body, performing various functions.

  • They're working at the levels of cells, constantly pulling and pushing stuff in and out of them to ensure that they work the way they're supposed to.

  • These changes are constantly occurring at the level of tissues cells coming together to form structures that performs specific functions which are constantly being remodeled in your body on their also occurring at the level of the organism.

  • You as an individual are also constantly changing.

  • You're responding to the environment both internal and external, and your modifying your behavior, your metabolism, your physiology to suit a particular kind of environment, right?

  • These kinds of changes are also constantly occurring at the level off communities, which means organisms coming together to perform collective activities.

  • The Ted X, I suppose in a vent, for example, is a community which is a dynamic community.

  • People are going to come.

  • People are going to leave.

  • People are going to come and talk.

  • People are going to sit and be part of the audience on.

  • So all biological entities are constantly in the state of flux.

  • So what biologists really spend all of their time doing is trying to understand how living systems maintain this dynamism right on.

  • How do they regulate this dynamism?

  • Because you can't let things run unregulated in a living organism.

  • But as you can imagine, change of any kind, particularly change that occurs with respect.

  • The time is incredibly hard to pin down simply because it's constantly changing right on dso.

  • You know, to just give you an idea off the kind of complexity that one is dealing with changes like this.

  • Proteins flopping around in a cell are occurring over time.

  • Friends frame frames about nanoseconds, whereas let's say humans evolving from apes is something that took millions of years to occur.

  • So a biologist is not only trying to capture change at these multiple levels of organization, but is also dealing with these vastly different time frames, right nanoseconds to millions of years, okay, on you know the pain off.

  • Looking at changing biology is that when presented with something biological, a biologist must look at it in the context off the changes that this entity has been true.

  • For example, if I were to show you a flower, it would be really easy to describe this flower in its current state, right, its shape, its size, its color so on and so forth.

  • But a biologist must look at this flower and try to imagine what this flower will be.

  • Once it's fertilized, it's gonna turn into a fruit, right.

  • This flower also used to be a mass of cells that looked nothing like a flower and could in principle, have given rise to pretty much any organ in applied.

  • This flower, evolutionarily speaking, wasn't a flower at all.

  • It was just a group of cells that performed some completely different function which have been shaped into its current form to serve a certain kind off property or function that this organ of the plant is supposed to play on.

  • So a biologist really can never dissociate from this constant change that biological systems are undergoing on, of course.

  • In addition to the slightly academic question off.

  • You know, understanding life understanding.

  • Change in biological systems also has its advantages in improving human health.

  • For example, an oncologist trying to describe trying to prescribe a treatment for a tumor will need to know what this tumor is going to look like over the next year.

  • If left untreated, right where this tumor came from, you know what it used to look like?

  • How fast it got to the point where it's got now so that the treatment regimen that's just that's that that is prescribed can be most effective.

  • I'm so so essentially understanding.

  • Changes in biology have academic value and, of course, also improving.

  • You know, our date really likes, right?

  • So having established that change is the only constant in biology, how does the biologist then capture change?

  • How does the biologists try to understand change?

  • Well, we do it much in the same way that a filmmaker, for example, tries to capture motion, right.

  • We essentially just take snapshots, right?

  • And if you pick enough snapshots, you should have a fairly complete image, a fairly complete picture off the biological entity that you're trying to study.

  • These snapshots could be photographs taken like this through a microscope or even without a microscope, or could be something slightly more esoteric.

  • For example, the levels of a particular protein, let's say, in your bloodstream or the levels of a particular protein in the cell.

  • They could also be things like the sequence off the D N A.

  • That make up your chromosomes and how that changes over time.

  • Or it could be the number of organisms of a particular kind in, Let's Say, a Week or a forest right tracked over time.

  • Until these snapshots, depending on what kind of question is that is being asked, can be a variety of kinds.

  • But essentially they're snapshots, and they need to be strung together over time to make sense off the biological system as such.

  • Okay, so, having laid that foundation for biology in general, let me tell you a little bit about what I do.

  • So I have a laboratory here at Icer Pony on Dhe.

  • I'm essentially a microbiologist, which means that I study bacteria well.

  • I studied primarily bacteria on DDE.

  • What I'm really interested to know is how bacteria undergo transformation from being antibiotics susceptible or antibiotic sensitive to antibiotic resistant right now, Several, if you will know that, aunty Bye.

  • Antibiotic resistance or an antimicrobial resistance is a burning by medical problem today.

  • You know, infectious agents that were that we could tackle about 10 or 20 years ago very easily with antibiotics.

  • Today we simply can't because several of those antibiotics have stopped working against these bacteria and trying to understand how bacteria undergo this transformation is therefore potentially going to help us to slow this transformation down.

  • So how do bacteria go from being drug sensitive to drug resistant?

  • Well, turns out that this process is essentially akin to what one calls Darwinian evolution right with, UH, a population of bacteria, which are drug sensitive to begin with, sensitive to the antibiotic to begin with when exposed to the antibiotic, eventually become drug resistant right on the way they do.

  • This is by essentially just enrichment off pre existing variants in any population that are able to withstand the drug better so the more drug a population of bacteria will experience, the greater the chance that they will become resistant simply because they've experienced that much more drug right on.

  • In that sense, India is at the epicenter of the M R crisis of the antimicrobial resistance crisis on Part of the reason for this is because off the just the quantum of antibiotics that get consumed in this country, right, Not only are we consuming a lot of antibiotics in India, but we're also using them up fairly loosely, right?

  • So the regulatory guidelines aren't as stringent as they should be on what this means is that we're essentially exposing bacteria pretty much anywhere.

  • You can think off to antibiotics, which raises the chance that they will eventually evolved to become drug resistant.

  • Right.

  • So what do we do about this in the lab?

  • Well, we do something called laboratory evolution, right?

  • Essentially simulating this process off transformation from drug sensitive to drug resistant in the laboratory so that you can study all of its bells and whistles, figure out how various things come together to lead to this change in female type off Delia on, then hopefully come up with a way off slowing this process now.

  • So how do we do this?

  • Very simple.

  • We start with ah whole lot of cultures off drug sensitive bacteria bacteria that will be killed by the antibiotic, right and then over time, because time is the only constant that we have under our control.

  • We we exposed these bacteria toe various kinds of antibiotics in various different ways to be able to mimic all of the different niches where bacteria may encounter antibiotics.

  • Right, And these are incredibly very in.

  • These are incredibly variable is I'll tell you in the next life on we continue to do this until these populations that we started off with which remember were drug sensitive have become drug resistant.

  • Right now, what we do is a bit of detective work.

  • We essentially traced back how this process occurred, and you no one can ask.

  • All sorts of interesting questions was with a single step process.

  • Was it a single step that took the bacterium from drug sensitive to drug resistant with a multi multiple steps involved?

  • Right.

  • How to changes in jeans?

  • How the changes in the sequence of the D.

  • N A.

  • That makes up the genetic material of these bacteria.

  • How does that correlate with this change in drug sensitivity to drug resistance?

  • One can also ask how environmental factors you know factors other than drugs contribute to this process right.

  • And finally, of course, are there ways in which by which we can slow this process down?

  • And that's really the the final goal of all of these endeavors to give you a quick, quick example off the kind off information that one can get from these kinds of experiments.

  • It This was a study that we did last year.

  • Well, we did over the last couple of years was published last year where we essentially tested how drug pressure's low versus hydraulic pressures influenced this evolutionary trajectory going from drug sensitive to drug resistant.

  • So what do I mean by Lohan?

  • Drunk High pressures?

  • Well, hydraulic pressures are typically high drug concentrations concentrations that are therapeutic that I used to kill bacteria.

  • These are the kinds of concentrations that bacteria would experience.

  • Let's say in your body, when you're consuming the antibiotic as treatment.

  • Like, uh, on the other hand, low drag pressures usually ah ah you know, are produced when dark concentrations are much lower than the little concentration of the drug, or when drug exposure isn't continuous right, and these kinds of environments bacteria will face in, you know, natural reservoirs.

  • For example, soil in water where there's anti about the contamination or even in your body when you stop consuming antibiotics before the course is supposed to have been completed right on drug concentrations.

  • Paper off, eh?

  • So we would essentially asking how these two kinds of conditions change this transformation from drug sensitive to drug resistant and what we found was pretty remarkable.

  • Don's out that when you have very high drug pressures, drug resistance does evolve.

  • But it evolves as a single step leading to a very heterogeneous mixture off bacteria, which are resistant to either high intermediate or low levels of antibiotics.

  • So you have all sorts of resistant mutants that you cannot do that you can isolate when you have lord drug pressures.

  • However, it turns out that this process is not a single step process.

  • It's a multiple step process involving these intermediates, which we call drug tolerant bacteria, which actually are only good at handling low concentrations of drug, that the concentration that they were facing, you know when they were undergoing this process of transformation.

  • But what's what's really scary about these intermediates is that when they do evolve drug resistance, they actually only river evolve resistance to extremely high concentrations of drug, which essentially means that imagine a bacterium that swimming around in a water body facing extremely low concentrations of antibiotic.

  • It's likely that this bacterium is going to evolve extremely high evolve resistance to extremely high concentrations of the drug without ever having seen those high concentrations of the drug.

  • And so you're infected by one of these bacteria.

  • Chances are that this antibiotic is simply not going to work as a therapeutic anymore, right?

  • And so So what this really you know, leads us to is a strong advocacy for what one calls antibiotic stewardship.

  • We simply cannot be consuming the kinds of antibiotics that we are in all of the various ways that we are.

  • Because antibiotics that everywhere at various levels and various concentrations and, you know, we may inadvertently actually be selecting for drug resistant bacteria outside the human body, you know, in the soil in the water that you're drinking in all sorts of places.

  • Anyway.

  • All right, so So let me let me quickly wrap up on DA summarize what I've told you today.

  • So I've tried to convince you that biology is essentially a new obsession with change we love looking at how biological systems are constantly changing, constantly dynamic on understanding this dynamic.

  • This dynamism off biological systems is part off understanding what it means for life to be called life.

  • These changes are inevitable, and they're necessary because biological systems must constantly change in order to adapt to the various environments that they're challenged by.

  • What have told you to a separate of my work is that the part that biological systems take to change is just as important as the as the end point right.

  • We need to We need to understand how these changes occur rather than just what that change is right.

  • And finally, one can very easily if one puts one's mind to it.

  • Link micro and macro level changes in biology together changes according at the molecular levels.

  • Changes occurring at the cellular levels at the organism level and so on and so forth.

  • And a complete picture of life off biology is only possible if we put all of these together.

  • I just want to leave you with ah thought, which is that you know, human beings are also part of biology, right?

  • And so the same forces that are constantly changing.

  • All other biological entities are also constantly changing us, right?

  • And so if we're going to understand ourselves, we need to take this into account and we need toe be cognizant of all the diversity and plurality that these biological forces of change are generating in human beings as well.

  • Thank you so much.

Okay.

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生物學對捕捉變化的痴迷|Nishad Matange|TEDxIISERPune (Biology’s Obsession with Capturing Change | Nishad Matange | TEDxIISERPune)

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    林宜悉 發佈於 2021 年 01 月 14 日
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