Prof. Nathan Gianneschi is a Professor of Materials Science & Biomedical Engineering at Northwestern University.
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Please send up to info at scientific sense dot. com. and. I can be reached at Gil at eappen Dot Info. Yesterday's Nathan Gene Ascii who is a professor of chemistry material science engineering biomedical. Engineering and pharmacology at Northwestern University his Associate Director of the International Institute for Nanotechnology at Western his Switzer spans by medical translation, polymorphic materials, making biological materials and advancing basic seclusive in nanotechnology Samedan. Very much for having me. Sure. Yeah. So I want to go through your papers. In more detail, but before you start. I would like to lay out a conceptual framework Toyota Research details. just very quickly needs, and I was at Pfizer in the ninety s not as a loser but as business guy and I will sit I used to think that former RDA in elegant. create decisions. The actually have no idea what they'll do once it's inside the body. So we go through many experiments, animals, and then humans in various faces to see what actually happens. At a show that too many people are not killed. There's a phase one study looking talk society closed and then. Tightly controlled doses there, and then we go back and look at efficacy. So. Then at least two thousand tuition rates in what what is called face to face to be in combination was about eighty five percent. which meant that only one in one hundred combines. Data Pharmaceutical Company ties actually succeed that process of human testing. Into market, and if you attritional just that the total expenses, it's about one point four billion per successful compound in the market. and I think in Twenty Years Since and attrition rates remained pretty much. The same costs have gone up about thirty percent more inflation, other the reasons, and so this process still appears to be somewhat inelegant. At least from my perspective so you have a little bit of a different approach to it. Right so did talk a bit about the platform that you haven't looked none. Yeah I think in academia as well. You have to remember we don't have the burden of always taking drugs to market and roundly. Take a taken and many others and approach to developing exactly that thinking about new platform technologies that could be eventually translatable. Certainly, that's that is a major goal. Main concern is in where can we innovate and in our case? where can we innovate on the material side? Material Science. Polymer Chemistry side. Where can we make impact? Where can we have an impact where maybe in the small molecule drug development world? Maybe even in other kinds of scale micro-scale formulations. A failed because if maybe trying to shoehorn in an old drug into a new formulation or as you've sort of alluded to screening lodge large numbers of drugs to some drugs that are already approved, for example, new uses. How can we stop breaking out of that and I think there are many many parallel efforts from all the way from the biomarker discovery? Weld. Through to the types of things we're interested in. Essentially in in the Biomedical Space What we've done a over the years is look at where I think a common thread as being looking at where there are biomarkers that have been identified as certainly by many other groups. For example ends. Up regulated a extra Selah Enzymes for example that are associated with inflammation, which is the basis of one about technologies. Rather than look at it as a target for drugging directly, and so this would be the traditional or even make quite innovative methods looking at how do we go off the drugging those enzymes selectively small molecules or even lodge kills antibodies, proteins, peptides. Than directly attacking those enzymes, how do we preserve them? They're they're part of the inflammation response and instead used them to target materials. and. In that way, you're not inhibiting the enzyme. You don't get any off target effects of that in addition process, which can be problematic actually in that case, because the enzymes present elsewhere in the body but rather use them to target a material, a diagnostic and a therapeutic and I think that that's been a common thread between both are cancer work and I work in in my cardio in function as well. It's kind of leveraged by Marcus and perhaps a different way. and. So so one innovation cares plant sport mechanism, right? Nathan. If I, understand correctly that the transplant can cancel with being really excited about an opportunity opportunities around hitchhiking on metabolic pathways again, associated with cancer, and in this case, it is a transparent process and this is from the point of injection. Of the material in this case of a of a molecule. Through to when it is taken into cells and tissues, and so again, these these are transport pathways that that a necessary for certain team as to feed themselves and so that feeding themselves quite vigorously with exogenous or in other words. Fats and proteins that come from the outside world and the outside wellbeing the other parts about body. So I bought another other parts of the organs that they're in. And so again, the question wasn't for us wasn't well, you know that'd be a lot of efforts she to drug those pathways. And in some cases to utilize them in that way to inhibit them, for example. So inhibit sort of the process by which cells and tissues cancer cells and tissues a trying to. Build the components to build more cells right to propagate the cancer. To maintain this high energy metabolism, high metabolism process instead of directly drug them use those channels has transporters completely orthogonal, completely unrelated anti-cancer drugs to try to get around maybe problems of drug resistance. To try to take. Maybe. Therapeutics that otherwise are somewhat limited in how much you can dose and try to change the game in that way so that that's been a big exciting you push for us. Okay so so so one focus there is. Sort of improving the therapeutic in. Right. So the difference between the toxic dose and effective does. And in conventional in Devi, just look at it, you know sort of the average population where those things are if you were to go into push slice medicine, lot of dickey's of freedom there but Certain companies. Kevin been really willing to do that yet but but I think your efforts In in the transport mechanism that you described and some of the new technologies in Manel materials that you will talk about is essentially getting to that right. So can we get a higher? Toxic does or lowered effective dose are essentially broad and that therapeutic index. That's the goal that's exactly right and and I think I think that that you know if you if you think of drugs that are very safe, we think of that as having this very large window between where it's effective. And that's defined some some some minimally effective. Response. For example through to where. You have tolerated though so a patient tolerance for it or An animal studies, the animals tolerance for for the drug, and so the bigger that window that the safer. But I think also that they recognized, of course that the the bigger that window, the more opportunity potential you have forgetting into sort of a new manifold of activity of the same drug. So if you dose limited if you sort of side effect limited in terms of the dose. That caps your ability to go after. The disease. In some cases right And in in certain traditional Chemo Therapeutics that is the the wisdom so. By by targeting the drug targeting a material that acts as a drug poke the that's that's where the game is to try to overcome those barriers and there are lots of very interesting drugs that have lots of off target effects. And so the whole field of even small molecule drugs. NANU scale carriers. There's lots and lots of labs really hammering away at this question of how do we broaden A therapeutic index, how do we open that window? Great Okay, and so if you take an existing agent. And if you piggyback on some process that you can identify, you can get to the target site. In a much more efficient fashion. In which case, you can turn the Turkic index right so that that's that's thinking packing on some process. But then also that nanomaterials that could utilize in that. Yeah. Yes. In the in the one instance that be the yeah. Like you said, the piggybacking on a process of say molecule consumption that's inherent to the disease and what you were saying earlier, that could be. Personalized in some cases or at least in. Batches of patients like certain types of GM, as at certain times, maybe metastatic disease, for example. So it might not be person by person, but it might be a market that's narrow down to a specific Close disease, for example. In the case of materials. There's lots of lots of work in the area and and the thought has been along those lines of what features that there are. Physical Features some of the. The wisdom around Leeriness of the tissue, the tendency of disease tissue to be maybe more indiscriminate about taking out Neta materials, and so there's been a lot of efforts in most that sort of space. Our purchase. Being. Really I think the the. What what's interesting is this idea of being out of retain materials for long periods of time as depots of drugs. And maybe diagnostics as well in the diseased tissue that being able to inject a material that's actually very relatively small and so. The the game is being very often played in the following way you make a nanomaterial that is long circulating or political or some kind of material that's long-circulating. So you get lots and lots of shots on goal right you're circulating long periods of time, and so every time you accumulate in the tumor. Our. Approach is really leant towards more towards an increasingly recently to materials that can be injected. Would circulate very rapidly unclear and they might say through the kidneys, for example, in optimal case. And instead what they're doing so that in other words they're below the renal clearance restaurant. So your body isn't seeing them as a nanoparticle it's not. What what happens often the NANNA scale particles materials seen as foreign entities. Almost yes. Same sizes viruses. By your system taken to deliver and destroyed, and so you got a lot of Olympic monolithic accumulation instead of targeting other disease other size. And so. What we've tried to do to say. Okay. Go Way below a low a small object ammonia, molecular weight species that assembles inside the disease tissue into lodge structure so that it can't come back else. Did, for example, in the case of a heart attack. Whether wound the injury I should say in the in the heart and the left ventricle. Is Considerable, it is leaky tissue it sort of open open windows. It's kind of like inflamed and open opened up the doors and windows to the vascular said, there's a way to get materials in. The vascular the trick is being to keep them in that and in our case by having them sort of expand their kind of expensive materials expand and get trapped inside they can't be pumped back out of the hot without success showing that fist step at least that were able to keep an accumulate materials. The next challenge for us is okay you can do that. Now can you deliver drugs and get a meaningful therapeutic effect? Can you get meaningful efficacy in terms of hot function and that's the next step. So that the annual bottles. So just talk a little bit about my infarction related work that you have done. So in animal models in in mouse models I guess Then you have an injury, there's lot of inflammation and you have shown that you can actually get materials to that specific site. And at can have a mechanism for those materials to stay there for awhile is that is that what has been accomplished? So they. So you're the in the the process by which you. Essentially have a blockage that leads to hot that the damage, right? Is a process that leads to obviously cell death. So this is muscle cell death. And then rep refute. So you blocking the blood and the blood coming back. Maybe, after surgery and so the patients recovering and their hot continues to go through this inflammation process, and so this is a process of rebuilding you think of scar formation on your arm if you've got to cut right. Same kind of process, rebuild the the the matrix that holds the cells together you propagate new skin cells, new muscle cells, and you try to heal the tissue. This is exactly what's happening in the hot. Except the The heart muscle is very poor. And see end up replacing the muscle with a lodge Scott. and. If that the the field is being in terms of driving towards tissue regeneration sort of biomaterials purchase a bioengineering purchase has been trying to grapple with. This is stem cell, other stem cells you could inject. anti-inflammatories and our if it's of really just parallel that and said, well, let's build a artificial scaffold within that injury. Where you could then release anti-inflammatories. Other components that may aid in the. Production of Newhall Titian with we've worked on that for several years. Now, with a a group WHO's really an expert in that area at UC San Diego Karen Chris Man who's in bioengineering that. So I've worked on that from these sort of two different angles together to try to address that through exactly that process. Okay, and so from my understanding, Nathan? So many use nanomaterials says it nanotubes of something like that Can you encase those things get the agent. you can you? Can you to drug agent inside the materials, right? So so the idea would be then through that, you can deliver it to August site. and. Easter any way you can control that externally. Interesting we've. We've there's a lot of interesting approaches to that, and so we've we've looked at. In our own work, we've really faded processes that. Controlled by the chemistry. So what we do to encapsulate the drug is connected inside Virus semi-permanent linkage that's degradable in the inside the the Olga. But yeah, the, there's some efforts to us You could target something and then use an external. Externally applied stimulus. We've favored sort of inflammation associated stimuli that has specific to the tissues, but you could imagine planting material and then addressing it said it from the outside world and people have worked on photodynamic therapy in the case of cancer. Using. Maybe ultrasound heating magnetic fields you could use, for example, a magnetic, quite strong magnetic fields and so. We don't do that kind of work, but there is sort of a rich ongoing a set of set of materials and studies in that area. Okay. Okay. You have people here. Related to the metal organic nine years. And so so so what exactly is a metal organic nanotubes? What are the use of that different from the typical? To upset you think about. This work. Is really an interesting direction for so we got very interested in. A particular set of questions that have come up a lot across all kinds of fields of materials science in chemistry? Of of all kinds of materials and that is mechanisms by which they form from the initial molecular components. To give these really lodged largest strumming the Nano scale but hodge structures compared to the molecules. What is the process by which molecules organize in order to generate micro nano micro, and then ultimately macro scale materials that we see in the world around us, and so these are sort of so-called seed in growth processes. Y-, Other? Molecules of become materials at that interface there's a lot of difficulty in. That process that people care a lot about materials of this type. And we've looked at others very similarly related go metal organic frameworks. General class of porous materials that really fascinating that have kind of taken the world by stolen Thames of lots and lots of interest across multiple failed where you're looking at storage of gases hydrogen gas storage maybe you look at catalytic processes say taking up smoking up co two There are programs that people looking at putting these at room temperature and soaking up water to trap water at the atmosphere. Just incredibly interesting materials at this very high surface area materials at kind of close. And we got interested for Alpar. We've we've collaborated with multiple up particular work was with a group at the University of Tennessee David Jenkins whose pioneer in that area of looking at this one dimensional tubular structure, all of those kinds of materials and they're really fascinated and whether or not you could make a single tube that would be like a chewable version of a carbon nanotubes covid nanotubes kind of have set geometry's he's his efforts of being well, could we could we blow that away by or out of the water by looking at shooting these things? You'd have like a Straw type material that you'd have to sickness Straw instead of being stuck with. The kind of chemistry you get maybe specifically from the the carbon and so they we kind of got together after a seminary gave actually university and I said look I think we might be directly visualized these for me. And we got excited about the possibility that of course, if you can see it for him, if you can understand how it forms then that informs how you synthesize it how you make this. Just classic cross routes way of thinking about designing syntheses as if I understand the mechanism than I have a way of putting it, and that's exactly what we started doing that study, which was to essentially video these nanotubes forming and it is videography but using an electron microscope, and that's where sort of Al Lab is interface with others on the more to fundamental synthesis and then ultimately applications and materials science. Has Been in the characterization of the types of systems. By visualizing them in liquids as dynamically moving by electron microscopy. So. These are still in the nine scale. So do you see more interesting application? So fit in therapeutic area yet just just an application. That would be we've we haven't thought about that. So we haven't thought of them as as as being immediately applicable and therapeutics, but they we we have invaded considered them at other absorbent materials as well as again frameworks of this kind of close I being look for exactly that purpose in some cases, they can encapsulate proteins, for example. which is really awesome where coming out of some colleagues of mine at northwestern and others where you know you can imagine stabilizing therapeutic for example, in these lodge pause that these materials have as I mentioned. This sort of Nana's sure idea would be like what we call and in the lingo host guest type interaction where the tube is a host and holds a chemical guest inside that can then ultimately have like a time release or a programmed release. That that hasn't been investigated specifically for those structures, but it is it is a field of increasing interest for show. Excellent we'll take a quick break. Come back, we'll talk about your walk into cancer. Thank you. Thank you. This is a scientific sense podcast providing unscripted conversations with leading academics and researchers on Righty of topics. If you like to sponsor this podcast, please reach out to info at scientific sense dot com. Via Back So so you have the people here, Nathan and this is about sort of the piggyback process that we talked about. Before and this isn't cancer. So this taxol, right? Along with the Human Serum Albumin Skirt and finding to get to the get to the cancer. Yes. Yes. So so The this this effort came about as a result. Sort of looking at again that that idea that. Could. We could we take some of these known biomarkers which up regulated the cells kind of putting out signals in order to consume something. So this is known for example, in a variety of different. Kansas for. Hormones being involved or. Some other kind of energy consuming peppis that might be present on normal tissues but more prevalent on. China's because of that sort of desire to grow foster, etc.. And so in this case, there's a receptor associated with. Many types during the process of setting up regulated consumption. Of. Fats. That sits on the cell surface. There are other receptors throughout the tissues that. Regulate and consume proteins as well, and so what we looked at in this case was. How do we hitchhike on? Not Literally what what's it was sort of a Trojan Horse Strategy Right? How do we trick the cancer? into taking out a molecule that is actually a toxin four let's aside a toxin. It will kill kinds of cells. It particularly affects cancer cells in it's very commonly used as you said, taxol or by its other name Paclitaxel. The approach can be generalized -able. So again, we sort of a favored the development of these types of platforms and so it could be put it could be used as A. Trojan horse can carry Greek soldiers. It can carry a lot of other things too. So, the concept obviously maybe. There's a time and a place for it. Once you've seen it once you get tricked again. But the team is do right they. They are kind of stuck on a pot like right we need to eat and they can rewire and they can become. Resistant to send Drugs and some of these are indeed resistant to taxations. Of Drug. People have tried to get around that in a number of different ways, and so one of them is to increase the dose and there's a lot of toxicity associated with these drugs so that we were talking earlier about therapeutic index. He's class of drugs work really well, there's lots of other platinum. For example, another cancer drug they they have narrow therapeutic indices, the narrow windows. Broadening those as being a big area of research and so. We thought bubble. Take that to the proof of concept drug If we can prove it for that it, it's mainly portable to other kinds of drugs. And it works and so that the idea is, of course that. what do we do differently I guess. What we did was we took the existing. Drug. Paclitaxel. We connected to a new kind of fat. That's a synthetic fat that has two ends to it one you can connect to the drug. The other end looks exactly like the native fat an put in specifically looks like stomach acid, which is a eighteen carbon long chain that is known in natural. It. To as you said, human serum albumin but that's just one part of the story. It also binds the transporters on the cell surfaces that transport in fats, fatty acid transporters. And so you've sort of engaged in without directly drugging you've engaged in the entire pathway in that way and we think. We've. Really. Excited to try to figure this along I mean how lab is a basic science lab with with We've got lots more understanding since that paper came out of mechanism of uptake. SCOPE in terms of different drugs Moving away from Paclitaxel to biological molecules, for example, in a whole range of things. But we've also started a company to go and try to pursue that because it it really needs to be done at a large scale and in a translation away and and so that's hopefully that's going. But yeah, that was the basic science question. Could you even use that kind of new kind of lipid to trick the system and it turns out you can. So we're pretty excited about. Yeah so so the trick there is designed the synthetic I guess it. So if you if you have the synthetic sort of piggybacking daycare, say if it has been, it has to be there has to be some advantage that it is taken up only by the cancer cell bright. Deport Askew extract an advantage and so yeah. So is it is it really the designers a synthetic? Click is going to be well it it. It needs to be biased towards the cancer tissue. So the drug the drug right now as given. Can go to all kinds of cells. That's where you get the off target problems and tolerated dose. So you could the perfect targeting system let's say doesn't exist today I could say, maybe it never will. You never want to say never. The perfect targeting system he would take the most drug. You can possibly find this that the field of antibody drug conjugates. Picking a really specific interaction between the cell surface maybe and and a targeting group like an antibody, and then guiding at very maybe low dose, the most toxic than you can possibly make. And and that's not really this gain. This is this is much more. I think. About biasing drug that already functions. At. Maybe a broad broad enough range that you can even increase it even further get access to this whole new. Level of activity, and of course, we're in mice. Oh, lots can go wrong. that. That's the idea and so yes, it's cold controlled at the level of synthesis. There's no. There's no weird. Trick, there's no we don't have any kind of unusual stimulus. It's not a nanomaterial it's. Good old fashioned synthetic small molecule chemistry and really looking at. ligand design. So how do you design molecule to look more and more like what than what the natural system is expecting to see? And this has been this Med chem game. Right? How do I mimic mimicking natural whole nine or natural ligand of the protein in order to Trickett into binding to my drug? And in this case, we use that game but instead to carry and Transport A. The bloodstream. And ended shows could results in the mouse model in several mouse models were were very, very well. including, some some other unpublished work that's ongoing We consistently see this effect of. You know. Almost. A twenty times increase in in therapeutic index are they might have been sixteen seventeen quote me on it. But then in a particular version of of of the studies and again I mean the the caveats here these xenografts animal models. There's sort of an initial first step for sure and as I said I, mean I think. Ultimately, this needs to be taken on and the proof will be in the pudding if you can ever get it to a human trial but certainly, very, very exciting in terms of where it could go. I think actually that the underlying thing is perhaps exciting for Paclitaxel. But more broadly exciting what it might be able to do for other drugs that aren't soluble that don't talk at all that have. Problems of target effects but otherwise beatings contesting promising drugs, and so we're very interested in working with the lives. The group's new drugs invigorating old drugs with with a fairly simple translational sort of technology. Santa Crafted meaning Nathan. Get using actually human tumors into into Moscow. Sorry for the Lingo the Zeno being forum. So it's a foreign graph of any kind but in the specific case, he has a human. Cheema. in a mouse. Model so the mouses immune system is compromised. That will grow a Human Jim. The other the other type by contrast is a mouse that that either spontaneously gets cancer or a mouse model that is used as a mouse cuma tissue that would be like an immune intact animal, which is a slightly more advanced model. Okay. Okay and so if you're successful you can see sort of the lower toxicity, lowest systemic toxicity but essentially the same level of hypocrisy as as the Asian currently provides. You Case. You're absolutely right that that would be great if he just decrease the toxicity and get the same effect. You would you would you be okay. What we actually get as a much better effect we can go much higher doses because it's so much safer. We can go to high doses, but we don't the key here was and we've done this before and actually failed with some Nano particles. We've made where we increase the safety on the high. End. The also increased the amount of drug that you needed to deliver. Right? That's not that's okay. But it's not really that exciting right because now you're seeing a lot of drunk. Right. You've just moved the goalpost, but it's sort of the same game. This is being this is a different story is where drug what's just as well as low end the load But we get a whole new level of activity at very very high doses and so because of safety which comes from targeting. And from some other factors. We're able to to to get to sort of a new kind of activity of the same drug. So it's I I like it. It's my baby. Someone will say. WanNa be right. You want to be in that real wide a window, not just a window that's moved to a high dose. Yes so eastern personalized medicine possibilities here Nathan could you actually ty tweet? to to get optimum. Yeah. It's really good question. We've been talking about this recently because they've been some really advances in understanding how these transport the fat transport systems are up regulated Dan regulated or changed depending on specific patients. Genetics said depending on the type of humor they have, and then a subclass of those as where, for example, they have a propensity become resistant. There's there's different types of some of these pathways unknown some of them have more recently being described and so. I'm never sure about. Talking about individual patient by patient but certainly, I, think narrowing in on. Patient populations where. People have been refractory so that they're not responding to A. Common. Commonly, given Khaimah therapeutic or other kind of drug all where you know that has become become resistant or that or a subclass of tumors you. Still you're still talking about you know these lots and lots of people. So it's not individual patients but I think being able to say you know, yes, you've tested positive for this this marker on your tumor and therefore this drug. Can Do something for you that other drugs con. I find a compelling and powerful thing for us to be involved in because obviously, it helps those people who otherwise copy helped. It's exciting. I wanted to jump into another paper in totally different area. So this is about Selena Melania. And and this video reason news I guess fight so. You'll finding some radiation protection for Selena minute that idea yeah. This is a really, really interesting exciting a fun project for us once again that's how baby. So we love it and. Got Interested several years ago in Mellon and. Melanin this call we sort of like to save since ubiquitous enigmatic. Material. It's almost every sibling. Every type of organism on some form of Melanin has been found. It's typically associated as being this black pigment or dark brown pigment. A associated with hair color, we find it in human skin. It's found in the brain of humans. Of the I, for example, an kinds of locations and there are organisms that use it as a pigmentation offer a variety of different purposes. For example, use it in structural coloration these beautiful area. Get Black Particle based it's a pure. It's like a an optical effective arranging black particles in space lots of beds do that the shiny even the Kovic so that blackout you see Cros obviously generated by them. noticed. They've got like Shimmery, bluish type of effect if you look at that. Fascinating aspects of Melanin. One of the most I guess interesting areas for the folks in the area is that yes, they are. They can prevent a damage from state radio housing radiation. So for example, And UV, for example, in the case of human since the imagine you know your skin becomes darker as you get you have sort of this impinging light which people call tanning. Process old buddy reacting to. The outside world insulting with UV. Radiation and. The what happens is that Carolina sites in your skin get sort of nuclei get coated in this black pigment. May Be absorbing some light but what it's really doing. is absorbing radicals that produced inside the cell, and so it's radical scavenger. Sort of a defensive. Exactly and obviously evolutionary early as well as as well as you know in humans and in in the case of protecting us from UV. But also used another cards and color-display by different animals that also has some thermal properties and it's a very interesting matera. But yeah. So we got broadly interested in one of the areas that it's shown up a bit as in. For example, not just V protection but potentially in protecting synergisms gamma radiation. So Higher Energy Radiation. And this has led some researches to look out for example, Kenneth protect patients during. radiation therapy. that's work from from several years ago from another group. And so we got interested in these questions of. You know UV higher energy radiation optimizing materials like this for those applications. And the should've fascinating question of whether or not different forms of Melanin that exist in nature. You know what to what degree do they protect? Two different amounts depending if? One of these other sub classes of Melanin. And so looking at it, we should have looked at one of the structures which is not as fail Melanin, which is a sofa containing Melanin, and we thought well, let's let's do what chemists do best and sort of move around the periodic table and so we moved. Down the verdict table to selenium the idea that you would get better attenuation oil better absorption of x rays. And ultimately potentially more radical content into the material as well. We sort of during the development of that we also noticed that we make a very, very close replica structure at least as far as we can tell of natural family element, which is the Melanin that gives people. That's president. People's have when they have read half, for example. So that that sort of led to this selenium material that we call Synthetic Melanin I. really standing out as it's really good x ray protector we did that in cells and human skin cells. And ultimately. Yeah. We we're excited by a couple of things. One is the applications which I'm happy to talk about The second one is this kind of what we kinda find interesting. Thought Process. Now, that will nature already made this. We made it in the lab from chemicals, but you know selenium the the compounds we used exist in nature. So the precursor US off founded nature. So it's possible that selenium based Mellon like this does already exists which is kind cool and and maybe it's new. To protect those animals from some process or maybe it's used as a depot selenium. And so so that's under investigation. And so so you mentioned X. So gamma rays hasn't been tested or you find it monarchy for we haven't done a serious test of these materials for gamma. Radiation Protection are we did x-rays because we have the source? UV. sort of underway but that's that's not really expected to be that beneficial the. Gamma. Brings out the other question and where we think there's some interesting applications potentially and not just protecting organisms like humans or maybe I'll scan as an application or something for space travel with. The materials and so. You could it be a lightweight coding, for example, and we've just sort of begun these discussions and I'd I'd love to have more and we're going to circle back with folks who are experts in. What it would take in terms of a shield on spacecraft or maybe even high out to cheat flight. and so those things of the beyond our expertise but happy to collaborate always looking for those phone calls around papers let. Reared fascinated by this idea that. You know that nature may be very well have beat us to the punch already be doing this. Yeah. Yeah. Not of people want to go to Mars Nathan. Increasingly. People money to go back to the moon. Moon. Don't WanNa line everything with lead right? Maybe you want some other cool thing about buying materials like this is you can produce you can coax organisms into making them. So we we had a bacteria. We went the Navy Research Lab. GROUP THAT COOKS BACTERIA INTO ACCEPTING selenium. Melanin inside bacteria. So you can imagine you could take some bacteria that you just have to feed nutrients, and then they make the material for you. So yeah, colonizing. Maybe. You stop thinking well, maybe if I could get a limited number of organisms to make a lot of different types of materials then I have a lightweight way of of building structures and things like that and that that's quite a provocative and I think increasingly interesting thought for people. Yet that that's very interesting. So one of the thought processes I think that you have to see. If you to go to, Mars, you have to see that. Fit Organisms. That would make something. But that also equally WANNA reward to all the radiation. and. So if he can create species cells organisms that are able to create something from a food and of change perspective about also resistant. Then northern climates of. Creating an closure. Goes. I think it's an interesting and and you know the these. Organisms in the melon melon is the organism clause. Particularly this we also work with this other kind of melon and called Allah melon. which is a type that's made by fungi some of these fungi being found on the international. Space Station around the Chenobyl power station site and and they believe to be yeah intrinsically resistant to at least low levels of radiation like that and even the presence of. Radioactive materials as well. So. Within their own. The, the sort of organisms on earth that was just radiation damage high temperatures these all. Sort of long been sought-after for how do they do it? Can we put some of genetic qualities over to other organisms? For example, one of the most famous of these kind of ideas was around you know using enzymes that propagate DNA from. A really robust organism. So you high temperature DNA synthesis, and so this concept of so-called extrema files, right organisms that have love and flourish under extreme conditions. Interesting and I think if you start thinking about space travel or maybe living on Mount Everest or wherever it is that you think. Is the most extreme environment you want to be there? Right, right. Yes. So so inconducive Nathan I know that you are doing lot of research in this area if the cross section of materials and life sciences. So, look forward five years. What are the things that you're most excited about and he predictions most successful? Would, they be. Sir We talked about a few few areas of our work and we've got some other sort of along the same themes one area that's really exciting for us on the on the drug delivery the broad question of drug delivery is. Know, whether we and and certainly people on the field and others than it be exciting to see everybody kind of progress towards being able to drug different types of disease associated interactions that have so far eluded small molecules and you kind of touched on that at the beginning of this process of small molecule drug development. This so-called sort of undrivable targets that I think some of the innovations that went out looking at in terms of hitchhiking on transport is. Getting, inside cells tricking tissues maybe indicate. Otherwise difficult to get a difficult drugs to get inside cells and tissues. BRECON crack that. You're talking and it's almost. That is the challenge cracking that barrier getting across these biological barriers. With some of these potentially powerful therapeutics. Will be game changing I mean talking about an a huge impact on answering kemp basic chemical biology questions about whether or not. You even want to drug those targets through to hitting really known interactions that drive near a generation they drive cancer, they drive the big unsolved diseases and Y- you're talking cancer heart disease Tissue Regeneration. Potentially a city neuro- regeneration that concept of in the context of diseases like Parkinson's. Huntington's these are the great incurable diseases driven by undrivable interactions and. We've got a big push towards at many many other people do and I think next five, ten years. It would be exciting to have that breakthrough I think be not seeing a big difference within the next decade. In Him and health. Yeah it's really exciting. So you know the conventional process as he knows your test compounds. Andy think about delivery mechanisms much later in the process. But what you're suggesting is that go back into discovery and preclinical and cab that transport mechanism integral. To, the the drug discovery process, it's not an afterthought. Deliver the agent, but rather it becomes integral to the discovery process which substantially changed. A. Lot teased on today I I, think. So and I think that's always being built in I think small molecule. Folks have been being built into the drug design right around rules around what can be done and what copy data not for a drug to be like a drug. But I think as the as the material science understanding of how to maybe Organiz those molecules in a different way progresses. Then those two sort of ways of thinking can work more hand in hand and and so I I do think there's an emerging opportunity in sort of the meeting of sort of by materials, material scientists, maybe Paloma, science, with some of these just a brilliant folks on the small molecule side to do exactly what you're. Saying you know people have been saying this for some time? It's that that challenge that idea is is one that's definitely on people's minds. Especially, as you start looking at these really difficult to draw difficult to talk diseases and I think the technology and our knowledge of these by Marcus has got to the point where I think we are on the cusp of that on the verge of it and certainly able to ask the question and before. Right. Yeah excellent. This has been great Natan thanks so much for spending time. Thank you very much for your.