The Bioinformatics CRO Podcast

Transcript of Episode 32: Ian Carroll

Disclaimer: Transcripts may contain errors.

Grace Ratley: [00:00:00] Welcome to The Bioinformatics CRO Podcast. My name is Grace Ratley and I’ll be your host for today’s show. Today I’m here with Dr. Ian Carroll. Ian is assistant professor of nutrition at the University of North Carolina, Chapel Hill, and his lab focuses on characterizing the microbiota in nutrition related diseases, especially anorexia nervosa. Welcome, Ian.

Ian Carroll: [00:00:19] Thank you very much, Grace.

Grace Ratley: [00:00:21] So tell me a little bit about your research. What are the goals of your research?

Ian Carroll: [00:00:25] I’m interested in how microbes in the gut influence the host. I’m extremely interested in complex microbial communities, which we tend to refer as the gut microbiota or the gut microbiome that you may have heard and how these influence the host specifically. I’m interested in how it influences adiposity. So that’s like weight, the accumulation of fat and also how it influences behavior so your levels of anxiety and depression. And right now we’re doing this under the context of eating disorders, specifically anorexia nervosa, because those patients exhibit dysregulated adiposity so they don’t put on and lose weight in the same manner as everyone else does. And also they exhibit high level of anxiety and depression. And we want to know if the intestinal microbiota within those patients influences the symptoms that are associated with their disorder.

Grace Ratley: [00:01:27] What is it like to work with the microbiota? What’s it like to study the microbiome?

Ian Carroll: [00:01:32] Well for me, the most exciting thing was, let’s say about ten years ago, maybe a little bit more now, a paper came out that, let’s see, the Godfather of intestinal microbiota research, Jeff Gordon, he published a paper based on the complex microbial communities in the gut of patients with obesity and how they changed when those people lost weight. It was only about 12 people in that study and what they used to do was use clone libraries to profile the microbiota. So basically you’re amplifying. In this case, it was the 16S gene and cloning it into a plasmid and putting it into the bacteria and then isolating it. And basically you would get 300 copies of the 16S gene per sample, which came from one patient. And that really, really fascinated me. It wasn’t just the fact that it was the intestinal microbiota and it was a disease. I wanted to know how you manage the sequences, what you did with them. And as someone who had never done something like that before, I don’t have a background in bioinformatics. I was just fascinated on how to do it. And over the years, I’ve become a little bit more knowledgeable on how to analyze those data.

[00:02:46] One of the biggest breakthroughs was Rob Knight, who created a platform called QIIME, which is quantitative insights into microbial ecology. And this was a platform for people with a very basic understanding of bioinformatics and allowed us to get ourselves into trouble I’d like to say where we would take some data and put it into this pipeline and try and work it out. And from there, I’ve had many students that have come to my lab and know a lot more about doing these bioinformatics platforms. And yeah, it was then that I started to get really excited about it and I was a basic scientist working in gastrointestinal division, so a medical division. I think it was the perfect place, the perfect time, because you have someone who is coming with a background in microbiology. There’s an emerging field of the intestinal microbiota. I’m in a division where people routinely work with samples that you can profile the microbiota with. So that’s where it all began for me.

Grace Ratley: [00:03:49] And the microbiota is what I consider to be a pop science topic. It’s very blog post-y, I guess, if you will. What is it like to work in in Popular Science? Do you get a lot of misunderstanding from people when you tell them what you work on?

Ian Carroll: [00:04:04] Absolutely, because everybody tends to know about the intestinal microbiota these days. And in fact, they always use the term microbiome. So the microbiota is the complex community of organisms or the living organisms in your gut. The microbiome is the cumulative genomes and genetic material associated with those microbes. So when someone says microbiome, are you sure you’re talking about the right thing? And in a way I guess it’s a double edged sword. It’s good because people tend to know a little bit about what you’re doing, but in another way, they tend to know very little about what you’re doing as well. To me, it wasn’t a popular science when I started, but it makes sense that the microbes that we’ve been living with for so long and are beneficial to you, that at some point they were going to become very topical. The most common thing that you would hear is, Oh yes, you work with the microbiome, tell me about the probiotics I should take. And yeah, that’s probably one of the most frequent questions I get.

[00:05:07] But for any scientist working in a very popular area, it’s good to a point because if there’s a lot of interest in it, you can get funding to do the work you want to do. But then there’s also what I refer to as microbiome fatigue, where when everybody is saying that the microbiome is associated with a disease, then it gets a little bit boring and you’re like, No, there’s no mechanism. No, you’re just saying that I’ve heard this so many times that could be detrimental to funding your research. So I think what we need to do is when we’re talking about the microbiome say, yes, okay, perhaps it’s associated with lots and lots of diseases, but we have to move forward and look at the mechanisms in which these microbes can cause disease and how they can be used as a treatment. And I guess in a way, your question is very appropriate. It’s good and it’s bad I would say.

Grace Ratley: [00:05:58] Yeah, I feel like there’s a tendency in pop science to overstate the ability of the thing that you’re studying. So people, they think, oh, if I take this probiotic, I can cure myself of irritable bowel syndrome. So what do you think about that? What can microbiota science do and what can’t it do?

Ian Carroll: [00:06:17] Let’s take a couple of seminal studies. So first of all, probiotics. There was a group in Israel that came out of the Weizmann Institute. And what they did was they were wondering about probiotic treatment after antibiotic treatment. So Grace, if you are ever discussing the fact that you took antibiotics with one of your friends, what’s the first thing they usually say?

Grace Ratley: [00:06:41] They ask if I get diarrhea?

Ian Carroll: [00:06:45] Well, that actually is one. But typically what I find is someone will say, Oh, you’re killing off your gut microbes, you need to take probiotics, right? Or you should eat lots and lots of yogurt. In that respect, this group investigated that, and what they did was they did a mouse study and a human study in parallel. They gave both the mice and the humans antibiotics a broad range of antibiotics to wipe out the intestinal microbiota. They repopulated both of them with microbiota like a fecal microbiota. They banked from one group, the others they gave a cocktail of probiotics and the other group, they let the microbiota rebound itself. The slowest group to recover their normal microbiota was the group that received the probiotics. So the probiotics were detrimental in allowing the normal microbiota to come back. The quickest of course was the colonizing yourself with what you already had, and then the middle group was letting it rebound naturally. So that’s a very interesting point about probiotics.Now, it wasn’t in the case of a disease. It wasn’t in the case of traveler’s diarrhea, which we know probiotics work for or pouchitis that we know probiotics work for. And then another seminal study that just came out again from the lab of The Godfather of the intestinal microbiota, Jeff Gordon has been studying malnutrition. I believe this study came out of Bangladesh where they had children suffering from mild acute malnutrition.

[00:08:13] And he’s been trying to develop, let’s say, a recipe for targeting the intestinal microbiota. And he’s referring to them as microbiota directed supplemental foods. Now, what you normally do in the situation of acute malnutrition is ready to use therapeutic food. One of them is termed Plumpy’Nut. It’s a very calorically dense food. And basically you give this much nutrients and calories to an undernourished individual as possible. So he took his microbiota directed food and the ready to use therapeutic food in two different groups. And refed these kids over time. The kids that received the microbiota directed food had received fewer calories. So it wasn’t as calorically dense. They got fewer calories and yet they responded better. They had better weight gain and better height for weight z-scores. So that’s telling me that you need to restore the microbial ecosystem and have a functioning gut in order to recover from something like malnutrition, which is forming the basis of my anorexia nervosa work because there’s certain overlaps there when you consider is voluntary restriction. But we’re talking about a dysfunctional gut. Targeting your microbes helps restore that gut function because what’s the point in eating all of this food if you can’t absorb it if your gut is not working properly. So there are two kind of seminal studies that I’ve liked in the last few years.

Grace Ratley: [00:09:51] So I know from working in your lab that it’s incredibly difficult to study anorexia nervosa because there’s not necessarily a good model for it in animals. So how do you get around that?

Ian Carroll: [00:10:05] You helped me get around that by working in my lab. I do it with two approaches. One is to do a human approach. One is to do a mouse approach. So as you said, with the mouse approach, you cannot fully mimic this disorder in mice. There have been attempts with the activity based anorexia mouse. I won’t go into too much detail about that, but essentially you create conditions in which a mouse will voluntarily exercise over eating. And to me, in a mouse, the only thing you can do is try to reproduce certain hallmarks of the disease that are relevant to therapy. For instance, we would use caloric restriction in mice and that calorie restriction is going to influence the microbiota and it’s going to influence the gut function. And they are relevant for therapy because as we just mentioned, we need a functioning gut in order to refeed individuals. So that’s one of the things we do. We take a specific trait associated with the disease and try and mirror that one trait in the mouse. The other option is trying to recruit as many patients as you can into a clinical trial where you can take multiple samples over the course of refeeding. We are very fortunate here at UNC because we have a center of excellence for eating disorders that was established by Dr. Cindy Bullock many, many years ago. We have eating disorders unit where we can recruit patients and get fecal samples over time as they recover.

[00:11:38] Now another approach that we use is gnotobiotics. So this is the term noto and bios, which are Greek words that mean known life. So essentially you’re looking at an animal that has their microbial environment completely controlled. So in this case, we have a mouse that’s grown in a bubble and a massive isolator. So they’ve never encountered a microbe before. What we do or what we have done is taken fecal samples from a patient with anorexia nervosa or a non eating disorder, matched control before and after clinical renourishment. Then we colonize the germ free mouse with those microbes and look at how they gain weight over time compared to the control group. And is there differences in how they gain weight at baseline and after renourishment. And also I work with another investigator called Lisa Tarantino, who we call the Mouse Whisperer, because she is able to do a battery of behavioral techniques. So we want to see if microbes from a human source can come into a mouse and then influence the anxiety and stress levels in those mice. So in that way, we’ll be able to tell whether taking microbes from a very noisy environment, which is the human and putting them into a very controlled environment, whether they have a functional influence on, let’s say, weight gain or behavior.

Grace Ratley: [00:13:06] Yeah. And I think that gets into the complexity of the microbiome because the microbiota they interact with the host and there’s a whole bunch of research on how they interact with host genetics and they interact with the foods that we eat. And there are all of these different variables that are incredibly difficult to control for. And so one problem that comes up in microbiota science is you get all these correlational studies, but it’s really difficult to pinpoint exactly what the outcome is caused by. So you see a lot of studies that link the microbiota to neuroscience or mental illness and to gastrointestinal disorders and all of these things. But how do we funnel that into cause and effect. It is really difficult.

Ian Carroll: [00:13:51] You’ve hit the nail on the head there with your comment about cause and effect. So those cross-sectional studies that you refer to, which I being transparent have been a part of, I think are important because the first step towards cause and effect, if you take a situation where you have a disease and a matched control and there’s no difference in the microbiota, do you move forward then? But if there is a difference, okay, now we can start moving forward. I mean, there would be an argument if there was no difference moving forward, but I won’t get into that. But it’s easier to say if there is compositional difference in the microbiota between those two groups, whether you can start exploring the mechanistic link between the disease and the microbes. And it is really complicated because we’re talking about numerous microbes in one system, which is your gut. That’s very different to another person, even though they may have the same disease. And each one of those has different genome, different genetic makeup, and may have a different arsenal of proteins that are producing decades influenced the host. So one thing that we do to move the science forward into mechanistic work is to try and use the platforms I’ve mentioned before, one being Novabiotics. You can transplant as I mentioned previously, but that doesn’t always work out. I published a paper recently where we took anorexia nervosa fecal samples and matched healthy controls and put them into germ free mice and we saw no influence on adiposity that is weight gain or fat mass.

[00:15:31] And we found several microbes that are associated with weight gain and fat mass. But it didn’t matter if it came from an AN patient or a healthy control. So there are certainly microbes that can influence your weight gain, but it didn’t seem to relate to the disease. There are new technologies where you can grow androids, which you take stem cells from the intestine of a human or a mouse and grow these tiny little kind of micro guts, and you can inject microbes into the middle of them. And if you have an idea like a gene from a microbe is influencing the host, you can knock out that gene in the microbe and then have a situation where you have the mutant in an android and the wild type in an android or even in a germ free mouse. The cause and effect, let’s take inflammatory bowel diseases. So in IBD you have a lot of oxidative stress in the gut. The motility of the gut is changed and you have an infiltrate a lot of immune cells. That’s certainly going to influence the any kind of microbial community. So can you really say that the change is associated with the disease or is it coming after so it’s consequence. But there has been a wealth of research done on IBD and how the microbiota, even though it could be changed by the environment, is influencing disease. So you could have a situation where it does change, but then ultimately it’s detrimental. So you can have a cyclical pattern.

Grace Ratley: [00:16:59] Yeah, it’s amazing to me how much we still don’t know about the microbiota. And not that amazing because microbiome science is so new. It’s not just new. It’s that even though we recognized that there were associations between the microbes living in us and our health, we just didn’t really have the tools to study them. And that really came with genomic technologies. So you’ve mentioned QIIME. Are there any other technologies that have enabled your research in microbiota research?

Ian Carroll: [00:17:31] Yes. So this is a really good point. Back when I told you about the story of the 316S genes per sample, it’s about $10 per sample back then to get each one of those reads so that’s 300 by $10, $3,000 for one person. It’s quite expensive. In my latest run that we used, I generated about 3 millions. So did I spend $30 million in my last experiment? No, I didn’t. And that’s because the technology has significantly changed and it’s all got to do with high throughput sequencing. And the first one came, it was the Roche 454 platform that used a technology called Pyrosequencing. It was still quite expensive when it first came out, but the main platform that’s used these days is the Illumina platform. Now there’s two ways you can go about it. You can use the 16S gene or you can do direct sequencing of a genomic preparation, and that’s whole genome sequencing. Whole genome sequencing will tell you everything that’s there, not just the 16S gene, but the types of genes it has in its repertoire. So you get a lot more functional pathways, metabolic pathways. You get all that information. With 16S, you are looking at one tiny little piece of a gene and trying to extrapolate that to the rest of the microbiome. And not only that, you’re looking at one variable region because the variable regions will tell you who is there. Both approaches give you taxonomy. So who is there and diversity measures how rich a sample is, but only the whole genome sequencing can give you the metabolic profiling, the functional genomics and all that information. The thing is with 16S, you can multiplex many samples. I do up to 300. I’ve talked to Rob Knight. He does up to 600 samples in one read which will make your sequencing costs maybe a bit $4,000.

[00:19:33] Whole genome sequencing you can multiplex. I only run about 20 samples on one run and that one run costs you $4,000. So if you’re doing many, many samples, it adds up really quickly. So traditionally, you’re going to see a lot of papers with the 16S profiling, which is really good. There are as you mentioned about technology, Rob Knight, a developer of QIIME also, I think it was him or someone from his group made PICRUSt, which is a platform where you can predict metagenomes from 16S data, which is very, very handy. And of course in certain samples where you can’t do whole genome sequencing, let’s say a biopsy from a human or a mouse where you’ve mostly mammalian DNA, if you directly sequence, you’re not going to get microbial DNA. So you’re better off doing the 16S approach. Now there are many new platforms that have arisen that at the time when QIIME came out and since then the RDP Ribosomal database project has their own mechanism for analyzing sequences. Greengenes is another platform, their data bases which are very valuable. They accrue all these 16S sequences and put them in their database so you can identify who they are. But QIIME itself, it wraps all these different programs into one easily usable platform. Many other people have contributed different programs that has been assembled into QIIME. So it’s just a dedicated platform for analyzing microbial communities. But if you’re clever, if you’re smarter than me, which is not too hard, you can use these programs independently through something or and do your own work through that and do your own analysis. And that’s becoming more and more typical these days to use your own personalized platform through.

Grace Ratley: [00:21:27] Yeah. So with the advent of all of these technologies and the decreasing costs, it’s put microbiota science in the hands of so many scientists, including people who want to commercialize it. I personally don’t believe that we’re really at the point of, since there’s so much that we don’t know about the microbiota, I’m not convinced that we can really commercialize it yet. I don’t think really anything demonstrates that more than the uBiome scandal that happened a couple of years ago. I don’t know if you have any thoughts on that.

Ian Carroll: [00:21:58] I had a collaboration with them and I would consider it the 23andMe of the microbiome. Basically they were giving us lots of 16S data. The collaboration was mutual. They were going to, when they sent out the kits, ask about eating disorder tendencies. And that would have been so useful for the scientific community. And we were about to receive all the data when something went wrong. And next thing you know, the FBI took all of their computers, so we didn’t even get those data. I have two stories that may answer this question for you. So as you know, I also work in a GI division, so at least the 23andMe can tell you if you’re prone to baldness or Alzheimer’s disease or maybe certain cancers. But that’s not there yet with the microbiome. And I know some GI physicians who would have patients come in and show them their uBiome report and say, my Bacteroidetes are low, what am I going to do? And this is nothing. I mean, what does it mean? They thought this would be the be all and end all of everything. So it’s not really there and just profiling something with specifically 16S just taxonomically. I don’t think it tells you that much. You can argue with me that it does. I’m happy to listen to other arguments about it, but what the Human Microbiome Project has shown is that even though we’re differing based on the types of microbes you have, the genes in those microbes are very similar.

[00:23:31] So I think it’s more important to have that kind of information. But you have to know the mechanism of how the disease works to bring that to the next level. And again, this is another commercial company. It’s called DE2.com. And this again was coming from the Weismann Institute. It was based on a study they did where they took a lot of people and they took a lot of clinical measures, blood, BMI, all those things. But one of the things they did was glycemic index, which is related to diabetes, and they did several types of analyses to work out what could predict the glycemic index in people. And it turned out it was an individual based combination of a few things, notably being a combination of certain components of the intestinal microbiota could predict your glycemic response to foods so they can tell you can eat ice cream and have a low glycemic index, whereas if I ate it, it could be quite high. I’m not saying that it’s real, but it’s there and it does something a little more useful than just profiling your microbiota, but telling you something biologically about yourself is a lot more promising than just you need to increase your Bacteroidetes. These technologies, I find them very exciting. I find them very interesting, but you have to be very careful with them as well as you move forward.

Grace Ratley: [00:25:03] Yeah, I totally agree. So let’s talk a little bit about you and how you got to where you are and at UNC and studying the microbiome and anorexia. So take us back to when you first became interested in science.

Ian Carroll: [00:25:18] I did my bachelors in Dublin City University DCU about a million years ago. I can’t remember now, but in Ireland what you do is when you’re in your final year, you work in someone’s lab, you have to. Back then I was working on a project that didn’t go anywhere, absolutely nowhere. But it didn’t matter because I isolated DNA. I made agarose gels. I ran DNA on those gels and I was like, Whoa this is DNA. This is brilliant. I was really excited by it, even though, again, it didn’t go anywhere. But the techniques and being in the lab and having the possibility of working on a bench as your job was just really, really exciting to me. So I went away for a summer and this is relevant. I went to South Carolina, so I finished my BSC and I went to South Carolina based on my girlfriend at the time’s recommendation. And I sold Frozen custard for the entire summer. While I was there, my wife and I, well, she’s my wife now. I got talking to someone and they said, Did you know about North Carolina? It’s the same kind of weather. It’s a nice place to be. And it has this research triangle park and you guys seem to want to be scientists. So this was really, really cool. And funnily enough, a hurricane came through at the time where we had to evacuate to North Carolina. So we got to see a little bit of it.

[00:26:43] So after that summer we had applied for PhDs, and it turns out my wife [Marie], got into Trinity College Dublin, and so did I. And we started our PhDs at the same time. A few years later, we graduated and were thinking about where we wanted to go. I had done my PhD in the Moyne Institute for Preventative Medicine under the stewardship of Professor Cyril Smyth, who is Scottish, and I was working on an organism called Helicobacter pylori. And when we’re talking about causes or consequences, this story kind of jumped into my mind because the person who discovered Helicobacter pylori was Barry Marshall and his supervisor was Dr. Warren, and they’re Australian. And no one would believe this guy that there is a microbe growing in your stomach. It’s too acidic, blah, blah, blah. Nothing, nothing, nothing. And he was convinced it was there. In the past, you had Koch’s postulates. Well not in the past, still today, but Koch’s postulates was a series of criteria you needed to fulfil to see if an organism, particularly a microorganism causes disease. And he grew Helicobacter pylori in a culture and he drank it. It colonized the stomach and caused gastritis. He isolated it from his stomach and he grew it, shows the same strain. And then he got rid of it with antibiotics and got rid of his gastritis fulfilling Koch’s postulates. And ultimately years later, he got a Nobel Prize. So that’s a very radical thing to do.

[00:28:13] But there you have your cause of consequence. But it’s not as easy as that with a complex microbial community. Anyway, I digress a little bit. So that’s what I was working on. And during that time we found that not we, but the community found that Helicobacter pylori has this injection system and it injects an antigen into the host cell which changes its shape. So Helicobacter can tuck itself nicely into the epithelium and avoid the harsh environment of the stomach. I was like, Whoa, that’s brilliant. And so I wanted to further investigate host microbe interactions. If we jump a few years back to when we were in South Carolina and we heard about North Carolina, myself and my wife, we sent CVS over to UNC Duke and I got an interview at UNC, and Marie got an interview with Duke, which was great. We came over and we got postdocs, and so we started here. I was working with a husband and wife team, David Threadgill and Debbie Threadgill, and Debbie Threadgill was my direct mentor because she was the microbiologist. And we basically worked on a microbe called Lactobacillus gasseri. So that’s a kind of a probiotic microbe, and we genetically altered it to produce a superoxide dismutase, which is an antioxidant with the idea that this probiotic, if in an environment with a lot of oxidative stress, it’s going to be able to neutralize it. And in IBDm, there’s a lot of oxidative stress.

[00:29:42] So we use the mouse model of inflammatory bowel diseases. This was a mouse model of colonic inflammation, the IL-10 deficient mouse, and we gave the wild type probiotic to one group and the mutant probiotic to the other group. And lo and behold, it had a greater effect on inflammation. And I was like, Wow, this is brilliant. And then at that time, when my postdoc was ending, I moved into the gastrointestinal division in UNC, and that’s when Jeff Gordon’s work started to emerge, and that’s when I hit it. Now, to get to where I am, it’s not just good enough to have these good ideas and have a passion for it because everybody has a passion and interest. But I feel that I benefited from a lot of mentorship and really good guidance. So there were people who I would say put their neck out for me, maybe thought they saw some potential in me. The first being was Robert Sandler, who was the head of the GI Division at the time, and then Balfour Sartor, who was my direct mentor. And basically what we did was we put a training grant together and I got this award that allowed me to become independent and work as a scientist under the guidance of Balfour Sartor. And then I met Cindy Bullock later on in life where we got interested in microbes and eating disorders, and here I am.

Grace Ratley: [00:31:11] How did your training as a traditional microbiologist color your experience as a microbiome scientist?

Ian Carroll: [00:31:19] It’s kind of a tough question to answer because when I was training as a traditional microbiologist. It’s very basic, you’re looking at, let’s say, a gene or a pathway or something in a pathogen. There’s a lot of work that goes into pathogens or antimicrobials is another hot area in microbiology at the moment. But basically you’re working at the molecular level to understand the machinery within that cell that leads to it being a pathogen or something else. And although I found that really fascinating, I kept thinking about what’s the clinical relevance of looking at this? What does it mean? And yes, I continued, and that basic foundation of my microbiology knowledge, although a lot of it is disappeared right now and how to do in vitro mutagenesis and transposon mutagenesis and try and find out which genes are associated with, let’s say, colonization of an animal. I really like but right now and I’m much more interested in the machinery, what does it mean to the human? What does it mean to a population? What does it mean to the influence of that microbe on the human? It gave me the understanding to be able to do the molecular techniques that gave me this stepping stone towards working in a clinical environment.

Ian Carroll: [00:32:42] And that meant working with human feces, knowing how to store it properly, knowing what to do if I wanted to transplant those samples into mice. So it was a perfect foundation. But traditionally most people would go down the basic science route of microbiology, whereas I was lucky to be able to chase what I wanted to do into the more translational aspect. And I guess my interest flourished being in the division of GI and Hepatology because I got to interact with physicians and they have a completely different way of looking at things than basic scientists. Although they are basic scientists in their own right, they’ve been doing basic science, learning their techniques, their thinking mostly about the disease outcome ultimately. And this kind of thinking is very much in line with the NIH mission. So if you’re looking for funding and you have your idea, if it’s in line with a clinically relevant idea, then you’re more likely to get that funding.

Grace Ratley: [00:33:49] So to younger scientists or scientists who are interested in going into microbiota science, what advice would you give these people?

Ian Carroll: [00:34:00] There’s just two routes because you don’t need to know the basic science if you want to get involved in in this field. There’s an emerging area where you’re epidemiology, nutrition and microbiome and that is quite exciting because you don’t even have to get into a lab. It’s the way that human genetics moved. Genetics started out on the benchtop, but now it’s all about statistics. Genome wide association studies like someone else can collect the samples. All you need to know is the data and you need to know how to put it together. And that’s one way that the microbiota is heading. Now, if you’re more interested in mechanism, then you’re going to have to get in on the bench and start working on it like that. But I would recommend is if you’re starting a postdoc or you’re at a stage where you’re ready for independence, I’d find a good mentor who has a good track record and has time for you. And they should be helping you develop your independent research niche. And to do that, they have to be willing to spend time with you to help develop it, but also maybe share some of their equipment, share their resources, and maybe their preliminary data and help you write a K award.

Ian Carroll: [00:35:21] So the K award is something that I had. It’s a mentored award for young scientists. It’s important to get into an environment that is collaborative rather than competitive. Competition just quells your interest in science I find. If you’re in an area where you can walk into a neighboring lab and talk to someone openly about what they do and there’s no secrets and they’re willing to share protocols with you, it’s just wonderful. Your choice of mentor is very, very important. I would also say I think it’s important for who you are to be represented in a mentor. So I’m not saying if you’re a white male, you need a white male mentor, okay? It’s the type of person you are. If you get into a, let’s say, a very well known college and they’re like, okay off you go, sink or swim. You could sink very easily. You need some support. And I think it’s good to be thinking about that when you’re moving forward.

Grace Ratley: [00:36:19] Outside of science, what do you enjoy doing?

Ian Carroll: [00:36:22] I have two children. One is 11 and one is 4, and they take up 95% of my time when I’m not in work. That’s another thing about work life balance. I’m the type of person who is not going to stay until midnight and not see my family. I don’t know anybody who would want to do that, even if you’re really busy. Okay, there are certain times where grants are due, but I always try and make time for being with my family, playing Transformers with the little guy, reading Harry Potter with the older girl. So what I really like doing personally and I don’t have a huge amount of time for it these days. But I used to devour science fiction. I would have hundreds of science fiction books read before the onset of Kindles and stuff like that. When I was walking around, I would always have a coat and I’d have a sci fi novel hanging out of my coat, so that was me. It’s also important to try and I think, stay fit. I don’t have as much time for as usual, but I have a trail right out behind my back garden and I can go out and do a bit of running and that keeps me a little bit sharper. Make time for yourself. Make time for your family. The ambition is there. But if it’s up to me, if I wanted to be the provost of the chair or something really big, I’m more happy doing really interesting science and spending more time with my family than doing anything like that.

Grace Ratley: [00:37:48] It’s really refreshing to hear scientists working on that work life balance.

Ian Carroll: [00:37:53] But once you’ve done your grad work, you should try and get your balance together and more and more people are having children while they do their grad work. When you have children, it’s really hard to do those long nights and not be there. I still see those people who do nothing but talk about science, nothing that dream about science and work all the time. And I’m like, okay, that’s fine, That’s fine for you. But I think it’s more important for young people nowadays to know that that’s not the model. I swear, sometimes I’ve spent those whole nights and absolutely done nothing. It hasn’t benefited me whatsoever, but being more focused and having better time to really, really work hard with a more disciplined mind is better.

Grace Ratley: [00:38:39] I couldn’t agree more. Thank you so much for coming on the podcast Ian. It was wonderful to talk to you. I loved hearing your perspective about microbiome science and about your journey becoming a scientist.

Ian Carroll: [00:38:48] It was great talking to you as well Grace.