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Transcript

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0:01Who are the characters behind science? This is Science Behind the Glass, Illuminating the Human Side. In this podcast, we unveil the human side of laboratories and science. Scientists share personal experiences, and we’ll discuss their meanings from different perspectives and fields of research. Welcome to Science Behind the Glass, Illuminating the Human Side, where we venture beyond the lab coats and data sets to uncover the human stories behind groundbreaking research.

0:32In today’s episode, we have the privilege of having Dr. Jacob Westaway, a bioinformatician whose work delves into the intricate world of malaria and the human microbiome. Jacob’s journey as a researcher takes us from the rush halls of academia to the far -reaching landscapes of Australia, where he is making waves at the Menzies School of Health Research at Charles Darwin University. With a keen focus on genomics and computational methods, his work sheds light on the population structure. and epidemiology of the cyanotic parasite Plasmodium, which is responsible for the malaria disease that affects both humans and monkeys in Southeast Asia. Jacob, thank you for accepting the invitation and thanks for being here. Thanks for having me. Okay, for start, Jacob, can you tell us what bioinformatics is and how it connects to human health research? Sure, so… I think put simply, bioinformatics is really just applying any sort of computational tool or method to answer biological questions, right? A lot of the time people would define it as like the overlay. So a few different intersect, I guess, I don’t know, sectors. So like an overlay of like biology, statistics and computer science, right? And I think a lot of the time when we’re talking about studying or like its relationship or the use in human health, we’re usually talking about using computational methods to interpret omic data. So like genomics, proteomics, transcriptomics.

1:59Do you connect the bioinformatics with the study of human health? Yeah, sure. So I think when we’re talking about human health, a lot of the time when people talk about bioinformatics, I think we’re talking about the use of computers to process genetic data, really. So obviously humans, like all organisms, we have an abundance of DNA, and that’s a lot of information. And so when we use sequencing or such tools, so essentially using wet lab methods to get… I guess, genetic information, we can’t process that information ourselves because we just don’t have that throughput capacity in our brains. Like we can’t look at millions of base pairs, which is essentially like the little bit of genetic components. So we get computers to do it for us. So they can process this stuff a lot quicker. And we can use things like high performance clusters that connect multiple computers together. So it’s super powerful, super fast. And that’s probably the main relationship I see between like human health or human health research. I think you get interested in these fields of research. Why no other one? I think the bioinformatics was definitely a necessity. So I sort of fell into my PhD. I didn’t go looking to do a PhD. I was looking for work experience. And this PhD project sort of just popped up in front of me. And they were like, do you want to do it? And I said, OK. And then once I started, it was like, OK, well, we need to. It was microbiome research, which is essentially you’re looking at the genetics of multiple microbes or small organisms that, in this case, live within the human gut. And you do a bunch of sequencing and you didn’t process a whole lot of biological data. So I had to learn and understand some computational methods and

3:30programming languages to process that data. So again, yeah, it’s just necessity for me. It wasn’t really an interest that I pursued. It sort of developed into an interest as I sort of got into it and started working on that part. But like when you said like the human microbiome, so it was just curiosity that took you to that part or how did you decide to use it? And what moment did you get that tip? into the bioinformatics and the connection that you did with the human bio? With the human microbiome, like there is, I mean, I guess previously, like maybe they could isolate a particular microbe in the lab and then culture it up and use that to study it. But realistically, when we’re talking about the microbiome, we’re talking about billions, if not more microbes, maybe not that many different species. Maybe we’re talking a thousand, hundreds of thousands of species, but like individual units, like individual cells or organisms, like it’s in the billions.

4:21And so you can’t… process that kind of information with without bioinformatics without computers so we can’t we can’t culture that many things and so how human microbiome or microbiome research really works is like you sequence a particular sample and you could do like targeted so you could you could target a part of the the dna of these organisms or you target all of it um but either way you’re churning out a lot of data and you need computers to process it and so i guess again like so that necessity to want to investigate the human microbiome which is really driven by my supervisors who are like clinicians and pathologists and they wanted to better understand the microbiome in premature babies um how probiotics are impacting them and things like that and then push me down that path and i guess i became interested when i started to see like the power of these tools i mean it’s kind of cool as well it’s like it’s like if you someone that likes cars or something like that and like powerful machines like like harnessing the power of uh Multiple computers, like hundreds of CPUs and all this RAM and like these big data sets. There’s something about it that’s like very enticing. And then starting to learn programming languages as well and see the power of writing simple programs to carry on very complex tasks. Like I think that’s very interesting and that really got me more and more interested in this field. Nice. And to talk about the other topic in your research, can you explain to us a little bit what is Madaria and why it is? a significant global health concern right now sure so so malaria is really it’s a life -threatening disease that results from plasmodium infection so predominantly plasmodium falciparum

5:53or plasmodium vivax they’re the two species that cause the most harm around the world and these plasmodiums so these small organisms essentially um are transmitted by mosquitoes to humans um and then the infection causes the malaria disease it can be very severe and life -threatening causes quite a lot of deaths every year so i think either last year or 2022 there was like a quarter of a billion so 250 million malaria cases again in the year and then maybe over half a million of those people died right so and that’s across 80 or so countries so just the sheer number of people it impacts right you can think about just the number of people that are affected um or that are dying but then beyond that like their families and those healthcare systems It’s a significant burden across 80 or so countries around the world. So that’s why it’s such a massive global health concern. But I think an extension of that as well, it also gets so much attention, not just because it is such a health concern, but I think because a lot of us think that we can tackle it. That’s why you see foundations like the Bill and Melanie Gates Foundation pouring so much money into malaria research because this is a disease that we should be able to manage.

6:57You see that it impacts Laura. middle -income countries more than higher income countries like you know australia has subtropical and tropical climates across the top with mosquitoes and you don’t see malaria floating around so if we can i guess bring resources to certain countries and better understand the malaria parasite we we can hopefully eradicate malaria and so yeah it’s not only is it a big global health concern but it’s a big research topic around the world as well because we can hopefully tackle it so i’m going to set the will they It’s a parasite and it’s transmitted for those mosquitoes. So it’s only one species playing this role worldwide or there’s many species? There’s tons. So Plasmodium falciparum and Plasmodium vivax are two species that are the main causes of malaria. And so, I mean, predominantly on the African continent.

7:40So Africa represents like greater than 90%. But then you have just a ton of different malaria -causing mosquitoes. And they don’t just affect humans as well. So, I mean, some of them only affect humans, I think. But we have like… simian parasites and stuff. So we have parasites. The one I work on is Plasmodium nolzi, which infects macaques. So it is a macaque host. They seem to be mostly asymptomatic and then it gets transferred to humans. But there are other ones like Plasmodium nolzi, Plasmodium malariae. And then if you get more into simian stuff, there’s like Ovale, Sanamolvi, Cogniae, Inui, Filviae. There’s a ton of malaria parasites out there. Oh, that sounds scary. You already explained a little bit what is human microbiome. But can you explain in simple words what is relevant in health and disease? And how is this connected? Yes, sure. So I guess just to reiterate, the human microbiome is essentially the collection of microbes that cause harm, right?

8:36And these are just like little microscopic organisms that are just like us but on a much smaller scale. And so I think the way to think about the human microbiome, I think maybe it gets lost on time in like human and medical research, but really logically it’s like this. tiny little ecological niche right it is this their own little ecosystem like within us and there are all these little organisms like a rainforest right and all these different animals that live in there and they’re all our microbes and that’s kind of what the human microbiome is except that there are probably a lot of different ecosystems on us right so the gut is the main probably the most studied microbiome in humans But then we have like a skin microbiome. We have an oral microbiome, nasal, pharyngeal, like everywhere. Essentially, we have these microbes living on and inside us.

9:16And we’ve co -operated with these microbes over millennia, right? And we’ve co -operated with them. And they are now at a point where they’re essentially integrated into our physiology. So we have this like sort of symbiotic relationship where we provide them with benefits, right? You know, a home, some nutrients through the consumption of fiber and things like that. And then they help mediate things like immunity and metabolism and even help. guide development early in life, right, for babies, which is, like, why my piece was on the premature infant microbiome. So, yeah, I mean, maybe just to simplify things, like, they are the bugs that live on and inside us and they are heavily integrated into who we are.

9:53We understand that connection with the human microbiome. We can understand how some diseases are developed and how to prevent some of them. Yeah, I mean, because they’re so heavily integrated into, like, immunity and metabolism, any sort of… I guess, alteration. And it’s hard to describe what that is because I think we quite understand exactly what kind of alterations in the microbiome cause what. But essentially, if you have some sort of imbalance, like overgrowth of the particular microbe or low diversity in your microbiome, so you don’t have a lot of microbes, you might have impaired immunity or metabolism or something like that because they are guiding those sort of systems in our body. Yeah, that’s right. So how do genomics and computational methods play a role in your malaria research and what advancements have they enabled in this field? Sure. So like I guess alluded to earlier, I said earlier that bioinformatics is really applying computational tools to answer biological questions. And so in the context of malaria, it is just using computers, at least in my context, and I guess in most of malaria, it’s using computers to process large genetic data sets. So, you know, genetic, transcriptomic, proteomic, metabolomic data sets. I think it…

11:04But for now, for the most part, it’s probably genetics in the context of malaria. For me and a lot of people in my space, I use these methods, I guess, to understand for the most part parasite genetics and then use this information to make inferences about biology. So the plasmodium biology, ecology and also epidemiology, which can then be leveraged downstream for public health, I guess, and more. So in malaria, a good example of like advancements or like using sort of bioinformatics is to identify and track. drug resistance, right?

11:32So we have a lot of drugs out there for the treatment of malaria. We don’t really have a good vaccine, but we can treat it. But parasites having a short replication cycle, so they don’t live as long as humans. And so the evolution can occur a little quicker, right? And so drug resistance can start to pop up as we treat certain populations. But with genetics, we can track that. So if we have enough ongoing genetic surveillance, so sequencing going on in different countries, we can see what drug resistance is popping up. And then we can start to to alter, I guess, the interventions in those contexts to have a better targeted intervention, right? Instead of just treating everyone with the same anti -malarial drug and certain populations, it’s not going to work because the parasites there will evolve beyond that. And so that’s probably the best example, I think, of using sort of degrading bioinformatics, genetics, and malaria epidemiology to come to something sort of constructive. That sounds really cool. Really tricky, though. Yeah, yeah. Can you share any exciting discovery or insight? from your recent studies that you have potential or impact in our understanding of managing malaria? Yeah, I think my particular research is still in its infancy. predominantly on plasmodium nolzene, which is a zoonotic malaria. It’s pretty understudied, I guess. So like I was saying earlier, plasmodium falciparum and plasmodium vibax are the big killers.

12:49They are the ones that cause the most number of infections worldwide every year. But what we’re seeing in countries in Southeast Asia, as we approach elimination of plasmodium falciparum and plasmodium vibax, we’re seeing sort of simultaneously maybe an uptick in cases of plasmodium nolzene, so the zoonotic malaria. And so that’s really been our focus. And I guess because it is such a novel area as well, there isn’t that much known. And so for the most part, anything we find is a positive contribution or something new. I think the most exciting thing that will probably come from our work, so something we’re working on at the moment is looking, we’re using genome -wide association studies. So essentially what that’s doing is looking at associations between variants and a particular phenotype. So in this context, we’re talking about an association between a variant in the plasmodium, so in plasmodium nausea, and also the severity of disease. At the same time, we’re looking for associations between human genetics, we have a human data set and severity of disease. And hopefully what this will tell us is what genetic components are associated, I guess, with severity. And hopefully that can help to, I guess, downstream develop sort of targeted interventions. At the same time with the human side, it’s like if we can understand why people are more susceptible, then it might help develop sort of better treatments as well.

13:58I guess that’s sort of stuff that’s coming. Stuff that we’ve sort of found, maybe like we have a… PopGen paper that’s coming out pretty soon. And I guess one of the interesting things that came out of that was that in low endemic settings, so settings where we don’t see a lot of malaria circulation, so like plasmodium nolzi, which is not as common as spousal supremum and vivax, even in those low settings, we see like the high risk populations. And so we could use genetics to characterize the number of infections or like specific plasmodium clones, essentially like individuals that are within an infection. And we can use that to identify certain people that have multiple infections. So they’ve been bitten by multiple mosquitoes. And you can imagine in an area where there’s not meant to be much malaria, you get an individual that’s getting bitten multiple times by an infected mosquito, that kind of rings alarm bells. And so what we’re showing with that is that there are high -risk individuals, right?

14:48So even though it’s a low -risk setting overall, there are going to be high -risk individuals. And in this context, because it’s zoonotic malaria, This is mostly people that work and, you know, do forestry work. They work in land clearing or agriculture. And so they’re in closer proximity to the monkeys. And so that’s probably the most interesting. I mean, there’s a few things. That’s probably one of the interesting things that I’ve heard about recently. So genetics can tell us how prone is the person to acquire the disease?

15:14I mean, in some sense, in this context, it’s more so identifying individuals that have very complex infections and then using epidemiological data. So we have data like… We know where these people are from. We know what work they do. We know where they live. And then looking through those different sort of that metadata and being like, okay, well, it’s very obvious that all these people with very complex projections are forest workers. And so that to us suggests, you know, at least the anecdote suggests that they are a high -risk population. That’s interesting.

15:45Yeah, it was pretty cool to see. Because, for example, with… Some mosquitoes, what they have found is like a bacteria that’s also in your cheeks or a certain smell that you release. They are more attracted also to that. I don’t know if it’s the same or not. So what do you consider are the biggest challenges that come with the application of bioinformatics in health research?

16:12I think it’s probably two things I think are the biggest. I think that it is a very… niche and specific skill set and like so for me for instance like i had to develop that skill set on my own because we didn’t have the resources where i was studying like they do now and they have some great subjects and but i think bioinformatics is this emerging sort of field even though it’s been around for a while and so the number of mathematicians is so small and so the number of people that can teach bioinformatics is very small and so for people to upskill it’s very difficult And then that’s amplified when you go to, again, lower middle income countries who don’t have the same resources as us. They don’t have the same infrastructure as us. And so I think it is, you know, the bioinformaticians, like this human resource is hard to develop.

16:56And it is really becoming like this bottleneck where we’re producing all this data, even in the context of genetics. Like we produce so much genomic data, but we have so few bioinformaticians. And so processing that stuff is becoming difficult because there just isn’t the people power to do it. And then I think the second thing. within bioinformatics is that you know you’re using programming languages like what people can imagine is that you have these files with these text files that have like lines and lines of code they process the data in different ways at different steps and you have to make a lot of decisions both like programmatically and maybe like even scientifically so statistically or mathematically as well and i think if you want science and to be you know reproducible and replicatable in this context like you really need to have that well documented And although those things are getting better, I think there’s still a lot of progress that needs to be made. Like resources like GitHub, where you have essentially a repository where people can install the code. It’s great.

17:51I think more and more people need to do this. I think this really is sort of, I guess, a hurdle that we need to overcome together as a field, for sure. Yeah. How do you see, for example, this new topic of artificial intelligence to overcome the first challenge that you mentioned there? the the manpower qualification that that kind of stuff do you think it will help for example in hospitals or something to automatize analysis or something like that yeah i think so like i think you like we already see like even like let’s say like in like free ai just like this super simple automation makes life so much easier like i was complaining to linda last week that i had a pipeline that i had to amend for a couple of different data sets but that like that’s an automated pipeline where essentially you drop in data and it runs and like so instead of doing like weeks of work of me trying to write something again and again i can essentially replicate the same sort of program and or code to carry out the same task and i think at the same time it’s like okay that that’s great it makes my life easier and so i can go on and do more work so that’s you know reducing the bottleneck where there’s all that data and less competition because we can’t automate stuff. But at the same time, like if you put something like that on GitHub, all of a sudden other people can use that, right?

19:05And it’s like, and then we’re all using the same tools, all using the same software. So that also helps to reduce the reproducibility and replicatability issue. And then I think with education, like we’re building that capacity or building biomechanics capacity in other countries. One, like having resources like that publicly available is good for people to come and use, but the upskill there is AI provides. so many opportunities like even using something like chat gp to help you get going at the start is going to be very beneficial like if you’re someone that needs to upskill um and teach yourself how to program using such tools to just figure out certain problems so you don’t want to get stuck for days or weeks on a program like it happens to us um like in this field for sure like all of us but less so now that ai is around and so i think if you are someone that is being self -taught those tools are going to make life a hell of a lot easier fantastic and What do you think that studying diseases and human health can be hard because it is something that touches directly? How do you feel that studying this field affects you personally? It is a source of stress or concern considering that for example the recent health crisis that we have with COVID -19. For me it’s no stress or concern but I think that’s probably like a personality trait thing. I’m quite pragmatic and a little bit stoic. Things don’t seem to worry me, but it still affects you personally.

20:25I guess the way it probably affects me personally is that I feel fulfilled. To work in a field like this, doing something I enjoy that I think is going to have an impact. If we go back to what I was saying about the impact of the burden of malaria worldwide, and we only work on a plasmodium that represents a small proportion of that, it feels good. to do things that you like they’re going to have a positive impact on people’s lives so i think is that how it affects me personally like that’s probably the most of that i could say yeah that is pretty nice because it’s a different focus that that’d be concerning you know everybody going crazy you know the next one and that kind of stuff yeah for sure i mean you can get stressed because it’s just reframing right you get stressed about it or you know like oh this is an opportunity for me to do something but i think that’s a good way to think about it and then Well, finally, what funny story or experience or maybe a horror story you can tell us about your career? Oh, that’s a hard one. I feel like I don’t have any horror stories. Like, I don’t know. I think I’ve had it very lucky and I’ve been pretty smooth sailing. Like, I think, well, okay. So one, like, I mean, there’s always data is like the big thing, right? We’re producing all this data. And even like producing programs and code, it’s producing like… essentially another kind of data right and so i’ve had it where i’ve lost lots of data and i think that’s probably the biggest horror story um and they’re hard lessons to learn unless someone tells you earlier about better ways of looking after your data and so a good example

21:56of that is like on the high performance cluster so when you’re working on a hbc or high performance cluster you log in remotely and you’re essentially writing programming this little black box like a little terminal right and you need to write little sort of computer code to tell it what to do and it’s very it’s quite simple unless you build like an infrastructure around that to make it a little bit more complicated um but early on i didn’t really understand anything and i remember i was just in a particular folder like if people think about a folder on your computer i was in a particular folder and i wrote this little command to delete some files in that folder and then it was taking too long and i was like oh this is interesting it’s taking too long and then i realized i was actually deleting my entire like everything i had on the high performance cluster so i was deleting all my data i was deleting all my scripts and i didn’t realize it was just taking so long it’s like this is taking a while and then i realized i was like crap crap crap and i had to stop it and then you know and i went back in and i deleted essentially the first half of like all my workflows and part of my data and it was just like oh okay but i mean the lesson there was it’s like always back up this stuff and so from there it’s like i have all my code on github i have all my data saved in multiple places just yeah don’t make that mistake So the message is please back up your data. Back everything up. Like everywhere. On SSDs, on hard drives, on like cloud, like everything can fail. Everything can have an issue. Just back it up for sure. Yeah, that’s the message.

23:18Back it up. Yeah. Thank you very much, Jacob, for accepting our invitation here and sharing your knowledge and your nerding. Thanks for having me. I enjoy sharing my nerdiness. This is a very interesting topic, especially to me. Bioinformatics is cracking the code of our gut microbes and how they influence health. And not only for humans, but for entire ecosystems even. This technology associated with microbial science reveals links between poor habits and diseases like cancer, heart issues, and even Alzheimer’s. Our previous guest, Dr. Osiris Gaona, mentioned how in the short term the study of microbiome will be personalized to treat particular diseases in individual humans.

24:07This is groundbreaking in medicine and is becoming more common in recent years. Yes, this is beginning to fulfill the expectations that arose with the Human Genome Project and this kind of initiative from the early stages of molecular biology. Also, something that is very important to bioinformatics is the inclusion of multiple variables. And we need to point out that usually we don’t see the processes as a whole, or we don’t have the capacity to do so. I mean, look at the microbiota, which can be affected by the food we eat every day, the environment we are exposed to, and our genetics.

24:41If we can see associations between those factors, we will be able to provide a better understanding of disease or even environmental problems. Yes, for example, deforestation disrupts natural habitats, leading to increased contact between human settlements and wildlife that can harbor diseases transmissible from animals to humans, like Lyme disease, malaria, and Nipah virus in deforested areas. Including this information can help us to treat diseases and find solutions to reduce health risk. That’s right. That is the challenge to generate the most complete model possible. This is a monumental task because to create good models and try to predict the behavior of complex systems, it is necessary to have a lot of available data that in most cases is not there in an accessible way.

25:28Yes, and the resources needed are expensive and specialized. You should have knowledge in coding and programming. However… There are bioinformatics online communities like Github, which share freely the packages and analyze complex data using bioinformatics packages. It’s also possible through blogs, ask questions related to errors and issues and find out decent guidance to use these packages. Yes, it’s great. And as in many episodes, we have seen how science finds transversal tools that connect knowledge as much as scientists. In this case, bioinformatics conjugate medicine, microbiology, and environmental sciences, among others. These kinds of tools have enabled people to face monumental challenges like the recent COVID -19 pandemic, to give a relatable recent example. And with this reflection about the human side of science, we reach the end of this episode. With this discussion, we close our episode for today. This episode was inspired by curiosity and the articles The Human Microbiome and its impacts on health. The other article, Deforestation, Avian Infectious Diseases, and Explosion of Bioinformatics Careers.

26:38We leave the references of this episode in the description. This podcast is self -funded and self -published by its host. Support us by clicking the like button and subscribing. You can listen to our episodes in Spotify, YouTube, and our official website. Follow us in our social networks on X, Facebook, and Instagram. Our original music by our colleague and friend, Bernardo Aguilar.