Hello, and thank you for listening to the Microbinfeed podcast. Here, we will be discussing topics in microbial bioinformatics. We hope that we can give you some insights, tips, and tricks along the way. There is so much information we all know from working in the field, but nobody writes it down. There is no manual, and it's assumed you'll pick it up. We hope to fill in a few of these gaps. My co-hosts are Dr. Nabil Ali Khan and Dr. Andrew Page. I am Dr. Lee Katz. Both Andrew and Nabil work in the Quadram Institute in Norwich, UK, where they work on microbes in food and the impact on human health. I work at Centers for Disease Control and Prevention and am an adjunct member at the University of Georgia in the U.S. Hello and welcome to the Microbinfeed podcast. We, your hosts, are blessed to have some excellent facilities for our research work, but some aren't so lucky. What is it like to work at the frontier? Today we have a special guest today, Phil Ashton, who is a bioinformatician at Malawi Liverpool Welcome Unit, based in Blantyre in Malawi, to talk to us about that. Phil, you've been working out of the UK for some time. Where have you been so far? Hi Nabil, thanks for having me on. My wife and I got married in September 2016, and I think three or four days later, we packed up our lives and moved everything to Vietnam, to Ho Chi Minh City, which is the commercial capital of Vietnam in the south of the country. That was a big couple of months. She had her PhD at Viva. We got married and then we moved across continents all within six weeks, I think. Why did you guys move to Ho Chi Minh? To escape the in-laws. Essentially, it was the last opportunity to do that while we were still relatively young and unencumbered. It was not really a rational decision, not a hugely rational decision. Again, this isn't what I tell fellowship application panels. It was all part of my master plan to solve a diarrhoea at the minute. Basically, I'd been a PhD for about eight years, between my PhD and postdoc. It's quite easy. You have a couple of kids or whatever, and you just maybe stay there for the rest of your life. Meanwhile, I decided to do something a bit stupid and quit our jobs and move to Vietnam to do a job that I found on Twitter. When you said you're moving to Vietnam, my first thought was, oh, you moved to Accra. You must be moving to work with Steve Baker because he does lots of bacteria. But no. It was actually Steve's tweet that led to me getting the job. He just said, does anyone want to come and work in Vietnam for six to 12 months on fungal genomes? In the same way that we wanted a change from living in the UK and everything, I was quite interested in fungi already. I'd seen a couple of talks at conferences and thought, basically, that the field was where bacterial bioinformatics was five to eight years prior to that, so really quite poorly developed. I thought it would be quite interesting to switch kingdoms before I got too old to learn new tricks. So, yeah, I changed to working on Cryptococcus meningitis, a fungal disease caused by Cryptococcus neopormans, primarily affects people with HIV. You turned out to be a very famous politician in Vietnam. I remember being in ASM NGS about two years ago, the last in-person one, and we all piled into an Uber and one of the people was asking, I think it was Kate Baker, was asking someone, oh yeah, where do you live? She's like, Vietnam. Kate was like, oh wow, I know someone in bioinformatics over in Vietnam. His name is Phil Ashton. Do you know him? And it turns out it was your wife. So famous, even my wife has heard of me. Yes. You're the only politician in Vietnam that anyone has ever heard of, certainly in that conference. Yeah, no, I'm just looking at her, I have her caricature actually that was done at that conference. I was there. I saw it in person being created. Yeah, I'm looking at it right now. It's a good conference. It's unfortunately virtual this time, so it won't be the same. But there was a glory kind of couple of years, wasn't there? There was IMM and ASMNGS and it just seemed like, and various hackathons and things. It seemed like we were all getting together all the time and having lots of fun in exotic places like Birmingham and Warwick and... Good times. ...Washington. Yeah. Very exotic. Inkston as well, don't forget that. Inkston, yeah. Inkston, yeah. I mean, Inkston, yeah, has its charms. Anyway, in Vietnam, you decided to have a bit of a family. How did that go? Well, yeah, it happened in the usual manner, I guess, Andrew. I probably don't want to go into too many details on a family show. No, thank you. Yeah, so we had the baby son, Joshua, was born in Vietnam. Lots of people go back to the UK or whatever to have kids if you're based at the unit there. Essentially, that means that we have to spend two or three months apart when my wife was very pregnant or when the baby was very small. So, yeah, we had the baby there, which all worked out okay. Vietnamese people love kids. They love babies. If you go into a pub in Vietnam with your kids, then basically the staff will just come and take the kid off you without asking and just kind of go and entertain it for 15 or 20 minutes. Oh, wow, that's brilliant. Yeah, yeah, it's great. And on flights and stuff, the Vietnam Airlines ladies do the same. One of the really nice things about Vietnam. And then you decided not to come back to the UK, but to move directly to Malawi. That's a pretty big move. So we moved to Vietnam for my job, as we've talked about. For the fungal work. And then basically me and my wife take it in turns to decide kind of which of us is, you know, who are we going to move for? Because we have the kind of classic two career issue. So my wife got this job as the lead molecular biologist at the unit here. So she's on a three year contract. So we're here for at least three years. And yeah, I just kind of managed to just sneak in before the lockdown hit and before Malawi cancelled all the international flights. So that was lucky. What is it like working over in Malawi? I know the unit over there will probably be very well resourced, but are you dependent on things like satellite, internet, generators for electricity, that kind of thing? So obviously I've been working from home primarily for the last six months or so that we've been here. Internet is 4G, Wi-Fi. So you definitely don't want to be downloading all of your BAMs for visual inspection. You know, it costs about a dollar per gigabyte. So, you know, you're definitely very conscious of data usage in a way you wouldn't be if you were in your office at the Quad Room or a PHE or what have you. Power cuts? Yeah, they have quite a lot of power cuts. When we first arrived, it's more or less daily. So basically Malawi doesn't produce enough electricity for its needs, especially... I think there was actually, they say that it's especially in the dry season because it's primarily hydropower in Malawi. And so when it's in the depths of dry season, obviously there's less water, so there's less electricity. So they have this delightful thing called load shedding, where basically they just cut off your power for six to eight hours per day. And I'd just like to have a brief side note that the slogan of Estom, the Malawian power company, is power all day, every day. Despite this policy of basically giving us power cuts every day, which goes slightly against the slogan, but never mind. That's nice. Most people, and us included, have what's called an inverter in your house, which is essentially four or five big truck batteries all wired together that goes through an inverter, I think, to convert it from AC to DC or whichever way around it needs to go, which powers most of the house, the low power things in the house when the power's gone. So that definitely takes a little bit of getting used to. You can't have the washing machine on or you can't blend up a smoothie while the power's down, but you can charge your laptop and your phone and stuff. And do you live out in the community or do you live in a compound? We live in the community. So we live in a very nice house that has been in the MLW family for at least 10 years, I think. People always come around and they're like, Oh, I came here when so-and- so lived here. lived here 12 years ago and basically one of the doctors at the hospital owns a house and when people are leaving, what we did when we were here for my wife's interview, we just kind of asked around, asked if anyone was leaving because a lot of the PhD students, the clinical PhD students, they come for two years and then they go so it's quite a constant kind of churn of people and so we just asked is anyone leaving and then this family were leaving and yeah so we just came around, saw the house, thought we liked it and that was good enough for us. That's awesome. Yeah it definitely helps not to be too fussy when you're, when you're, when you kind of live in other countries. I think that people who are very particular I think would have challenges but we're quite easygoing so most things are okay. And in terms of actually getting mathematics done, do you have a data centre on site or do you do everything in the cloud or what? Yeah I do everything on the fine, fine MRC Climb or MRC Climb big data resource which is absolutely invaluable to my work and I just like to give those guys a shout out. Could you write that down please? I'm one of the co-eyes on the grant so could you write that down so that we can you know use your testimonial? Absolutely yeah happy to. Yeah I try to always reference it in papers but maybe I should double check. But what about internet connections because using a terminal you know for such a long distance particularly over say 4G must be quite frustrating. Not really so Malawi you know is such a different setting to Vietnam. Like Vietnam very obviously a lot of challenges but really rapidly growing economy. You know life is getting better for most people every year like year on year. Everyone has a 3G, 4G phone, everyone has a smartphone, everyone's using it all the time but Facebook and YouTube and everything. Whereas Malawi I think it's only 8% or 11% of people actually have power in their homes. So you know the networks are not super busy and we're kind of pretty close to central in the middle of the kind of commercial capital. So the network is actually very good and probably better than it was in Vietnam for the 4G network. So usually I've got the speeds like 50 megabits per second or something like that. It's actually faster than I have here in the UK near Cambridge. Yeah probably a bit more expensive as well but yeah I've got no complaints there really. And again we don't have any sequencers at MLW. So I usually have to go through various loops to avoid downloading data to my local computer because you know it's good enough for SSH and for web browsing and stuff but any kind of you know no I don't want to be downloading you know Kraken GTDB database. It costs like £100. You have to be a little bit cautious. And what organisms are you working on these days? So my bread and butter is Salmonella typhi. Yeah Salmonella typhi and Salmonella invasive non-typhoidal Salmonella. So I'm working with Professor Melita Gordon who's worked on these organisms for at least around 20 years I think or so. She's a clinician researcher with an interest in vaccines. Yeah she's done this massive study immunising 30,000 kids against Salmonella typhi with a new vaccine and then they're doing lots of monitoring to check whether the vaccine has been efficacious. So that's producing lots of Salmonella typhi isolates which we're going to look at for sequencing and with sequencing and there's some drug resistance issues and then a nasty XDR Salmonella outbreak in the in the pediatric nursery at the hospital as well the Queen Elizabeth Central Hospital that we the MRW is affiliated with. Is that the same XDR that they have in Pakistan? So that's an XDR non-typhoidal Salmonella. Basically South Asia is way ahead of us when it comes to drug resistant typhoid and actually it's quite funny because clinicians and everyone if you come out here and you've worked in London say then in London most of the typhoid is from travellers to the Indian subcontinent where it's all ciprofloxacin resistance or it's almost all ciprofloxacin resistance whereas in Africa cipro resistance is much less of an issue and actually typhoid historically in Africa wasn't a major issue it's only more recently that it's become an issue and so you come here as a clinician you might come here and think oh well you know why is it such a big deal you know they're talking about a cipro-resistant typhoid like all typhoid is cipro- resistant isn't it but obviously if that drug resistance gets into the population here then that's just gonna make an already bad situation even worse. So how do you do your typing for Salmonella typhoid? I use Phoenix I think maybe I'm the only person outside PHE that uses it but yeah I use the PHE kind of pipelines to go from reads to SNPs and then the consensus master and then I use SNP sites to extract the SNP positions and then you know phylogenetics yeah shout out there and then yeah genotyphy yeah actually Cat people from I'm collaborating with people from Cat Holt's lab so for many of the typhoid they've already run genotyphy on it before I get there so. That's awesome. I'm using genotyphy now in my projects so it's if I didn't know about it if I didn't find it on my own just through github search I would have just found out about it now. Yeah I love those kinds of projects you know the ones that let us all kind of speak the same language when we're talking about clades and such and I've always been very glad I've never had to write one myself. Yeah I was thinking about writing it and then I found it so thank you Cat Holt's group. Yeah and just identifying these like SNP barcodes and everything that you have to find to do them just seems like a bit of a headache. Your bread and butter right now is typhi. I don't know if this kind of is in your universe too but in my universe usually I have kind of like the mission of the organization and then I also have my academic interests so if that's the same with you is there it sounds like Salmonella typhi might be like the overriding mission. Do you have like an academic project also? So I'm on a one-year contract to start with so I got very lucky essentially you know we came here for my wife and then I collaborated with Jay Hinton at University of Liverpool previously who's a close collaborator of Melita and so kind of via that I got a one-year position. You know at my career stage I'm kind of thinking I'm looking for the transition to independence as they say with a fellowship application probably and at the moment I'm thinking about E.coli, diarrhea which I quite like for a number of reasons partly because it's just a bit it doesn't really it's not currently it doesn't have a nice story you know E.coli, diarrhea. I think Andrea have you done you've done some E.tech work right? Yeah I have in fact I just submitted some assemblies only a few days ago for E.tech. What's your now I've got you out here actually what's your kind of take on E.tech? I don't know it always confuses me. Yeah good I'm glad you said that otherwise my first application would be pointless. So E.tech is the traveller's diarrhea and I think I've gotten it a few times you know having gone to places like the Gambia and whatnot. We had an E.tech paper I think now a couple years ago the first author was Vaishnavi from our lab she's since moved on to hospital acquired infections but she did a pretty good global E.tech paper and I think it was a very difficult topic because maybe it's confusing because not a lot of people touch on it like S.tech or V.tech are the more public health impact things but I think E.tech is maybe not as viewed it's undervalued right now in the literature. I've just done a paper with Astrid von Metzer and she has got eight different lineages defined for E.tech and has done you know beautiful hand curated reference genomes and hand annotated reference genomes and so it's quite nice defining all those lineages it's based on some earlier work she'd done on a kind of a large-scale study. Yeah yeah she did the kind of found oh she was the first. author on that kind of foundational nature genetics e-tech paper back in 2014. But yeah, it's essentially just a bit kind of, you know, obviously some people, those guys in Sweden have done some work and people have done, I think Jason Sahl and sounds like CDC have done some as well, but essentially it's just not super well defined and not super well characterized, especially not in terms of a deep dive in, you know, a single high burden country. Yeah, I'm thinking about e-tech and maybe even doing some immunology if I can find an immunology immunologist to collaborate with. I think we focus on enterohemorrhagic E. coli because we've got the elephant in the room of O157 and that's fairly clonal and your ST131s as well, like they're there and they're well studied. But I don't think there is such a dominant pathogenic clone in e-tech, is there? No, I guess Andrew probably knows the latest. I'm working on Astrid's 2014 paper. This is where I say I'm a computer scientist and I will claim ignorance. Well, I mean, someone, there's like eight different lineages, right? Yeah. And they all have these different virulence gene constellations and you find it in healthy kids and in sick and in kids with diarrhea. So maybe I'll do some pathogen GWAS, look for genes associated with sickness rather than health. Yeah. So kind of run a big prospective study and collect a bunch of stool samples from healthy and sick kids, obviously with all relevant ethical conditions in place. So you're kind of giving away your fellowship here and someone might be listening and just type, you know, skip it. He's also advertising because he was able to advertise on the podcast for a collaborator, maybe he has an advantage here. The micro bimfy bump. Yeah. I'll definitely mention you guys in my Nobel if we get the e-tech Nobel. But I just find I haven't got much time for like being secret with ideas. I'd much rather mention them to people and talk about them. And I don't want to say ideas are easy, but delivering project is hard. Coming up with an idea for a project is not the hard bit of the project. Right. Yeah. Especially in E. coli, there is so much on the genomic side to do. After your family's three years are up, if you are going to a next country, because you might still stay there because it's such a beautiful country. But if you went to the next country, what's your next target? Yeah. Tricky one. I do like living in kind of exotic and interesting places, but sometimes you also just want to go to Mars and Spencers. There's a lot of countryside in the US, especially around us in Atlanta. Yeah. Basically what happened to us in Vietnam and Malawi, I was never, oh man, I really want to go and live in Vietnam. And then, oh, I really want to go and live in Malawi. The work definitely brought us here and that's awesome. And I love both the countries, but I'm not kind of, I haven't got like a list of countries I want to live in. I just think that I'm kind of fortunate that we both do jobs that kind of take us to interesting places. And I'm kind of, I'm pretty open-minded really. If someone said, oh, you want to do a faculty job, a tenure track job in the US or Australia or UK, then I'd probably do that. Or, you know, if someone said, oh, do you want to go and work in South America and, you know, do kind of continue the work in high burden countries, then yeah, I'd be pretty interested in that as well. Have you been doing any COVID work, by the way? Zero, zero. I was all braced in Vietnam because obviously very close to China, lots of connections with China. And I thought, you know, it's going to kick off in Vietnam, like before it kicks off anywhere else. And obviously Vietnam has just gone and been all competent and business-like in their public health response and put the kibosh on that. So my wife does nothing but COVID. So yeah, Vietnam's done incredibly well. So we're doing a project with Zimbabwe at the moment, and we have gone and sequenced 97 genomes. So this is kind of the first public announcement of it. So yeah, 97 genomes, and we found some kind of interesting stuff. But of course, you know, when you share a lab, it can be hard to keep things out, particularly when they're maybe porous and that kind of thing. I mean, I guess they're just trying to slow the inevitable. But, you know, there's this kind of big mystery as to why the mortality in Africa seems to be relatively low, even after accounting for the different age structure of the population here. Basically, there was a thousand bioinformaticians who knew more about COVID before I got anywhere near it. So I just kind of made an emotional decision to not really professionally engage too much. Thanks, Phil, for joining us today. We've been talking about bioinformatics at the frontier where things might not always be reliable. And yeah, I'd like to thank Phil for joining us today and see you next time. Thank you all so much for listening to us at home. If you like this podcast, please subscribe and like us on iTunes, Spotify, SoundCloud, or the platform of your choice. And if you don't like this podcast, please don't do anything. This podcast was recorded by the Microbial Bioinformatics Group and edited by Nick Waters. The opinions expressed here are our own and do not necessarily reflect the views of CDC or the Quadram Institute.