Portal de Periódicos da CAPES

Britt Koskella

2017; Elsevier BV; Volume: 27; Issue: 23 Linguagem: Inglês

10.1016/j.cub.2017.10.058

1879-0445

Britt Koskella,

Insect symbiosis and bacterial influences

Britt Koskella obtained her PhD in 2008 from Indiana University, where she worked with Curtis Lively to test for a role of parasites in maintaining host sexual reproduction and diversity, using experimental coevolution of the New Zealand mud snail and its trematode parasite. She then received a US National Science Foundation postdoctoral fellowship to work with Angus Buckling at Oxford University and John Thompson at University of California, Santa Cruz on the interaction between bacteriophages, bacterial pathogens, and plants. After her time in Santa Cruz, she returned to Oxford and then moved to the University of Exeter on a series of UK Natural Environment Research Council fellowships. During her time as a research fellow, she examined the role that phages play in shaping natural microbial communities living in the phyllosphere (above ground tissues) of the horse chestnut tree, as well as the link between the tree microbiota and disease. Koskella is now an Assistant Professor at the University of California, Berkeley, where she combines molecular approaches and experimental (co)evolution to examine microbiome-mediated protection against disease, the importance of microbiome transmission among generations, and the role of bacteria–phage coevolution in shaping the microbiome. What turned you on to biology in the first place? Science was not my favorite subject at school. I enjoyed the laboratory sections (apart from dissections) and liked learning about how the world works, but never saw it as a career option. During my first two undergraduate years at the University of Virginia, I was a Psychology major and hoped to go into research in the area of human behavior and cognition. However, as time went on I became more and more frustrated by the reliance on correlative patterns to test hypotheses. At the same time, I began work as a part-time research technician in the laboratory of Janis Antonovics, whose group was working on the beginning stages of a host shift in a sexually transmitted plant pathogen between two co-occurring Silene species. In addition to learning numerous new molecular and experimental methods, I was also included in lively lab-meeting debates on new theoretical and empirical work in disease ecology. This exposure opened my eyes to the power of experimental biology in general, and to experimental evolution in particular. I was then given the opportunity to undertake an experiment comparing the impact of pathogen-strain relatedness on coinfection success (Koskella et al. (2006) Am. Nat. 168, 121–126), at which point I was convinced that science was for me! The realization that a carefully designed and properly controlled experiment could help answer biological mysteries, such as why organisms sexually reproduce when clonal reproduction is so much more efficient, was eye-opening. I began to seek such questions out wherever I could, and suddenly the world looked a whole lot more like a recent crime scene, with tantalizing evidence, and a whole lot less like a textbook. What aspects of your research are you currently most excited about? This is an amazing time to be a biologist. The more we learn about the microbiome, the more we appreciate its involvement in every facet of life, shaping host health, interactions among species, both micro- and macro-evolutionary change, and even ecosystem function and resilience. The applied angle of microbiome research is only beginning to come to light, but already there is promise of, for example, increased drought and pathogen resistance in crops, as well as clinical success stories of microbiome transplants in humans to treat disease. In my own work, there are two exciting leads we are now following up on. First, we are moving towards a better understanding of how bacteriophage viruses shape the microbiome, including during initial establishment and transmission among hosts. We are using tomato plants as a model system in which we can take either a community-level approach by ‘depleting’ phages from the microbiome as a whole, or a more controlled approach by piecing back together pairwise interactions between bacteria and phages in synthetic microbiomes. Together, these two approaches will help us uncover how phages impact upon microbiome diversity, composition, evolution, and ultimately host health. Second, we are working to build a predictive framework for characterizing the protective effects of the microbiome against pathogen colonization. We have recently published correlational data from horse chestnut trees across the UK that show bark microbiome composition is associated with the bleeding canker disease caused by the pathogen Pseudomonas syringae pathovar aesculi (Koskella et al. (2017) New Phytol. 215, 737–746). We are now using the tomato system to test the underlying causation of this pattern: is it that disease leads to a shift in the microbiome, or is pre-existing variation in microbiome composition predictive of disease susceptibility? If the latter, we hope to leverage this pattern to build better synthetic communities that confer plant protection against pathogens. What parts of your job do you value the most? I most value the chance to work with remarkable and talented people and the fact that I get paid to be creative. I often think I have the best job in the world, despite the constant stress of being behind with deadlines. First, I get to engage with incredible colleagues and have the privilege of mentoring and advising amazing and enthusiastic students and budding researchers. By far the most rewarding part of my job is seeing these students and mentees succeed and develop their love of science. The drive to answer questions about how the world works unites people from all backgrounds, and it is very rewarding to hear or read about the diversity of approaches and ideas being tested to address the same big questions. I also enjoy that I am able to shape my own goals depending on which research leads I feel are most interesting and exciting. Although grant writing can be a slog at times, I love sitting down and brainstorming the best experimental design to answer a particular question and to think about all the things we still don’t know! How do you decide what research to pursue next? Reflecting on the studies I have done that I am most proud of, it seems many of my most exciting scientific moments have come after I’ve been thinking about a new question or study system or, in the most extreme case, switched fields. In these cases, I’ve had the opportunity to sit down, read deeply, and really synthesize the literature with fresh eyes. This allowed me to identify important gaps in our understanding of foundational topics, and also to think about these problems with a level of naivety that I feel can be important. Sometimes, when we are so deep into the trees that we can no longer see the forest, it is easy not to embark on a new direction due to fear that it’s too high risk or too ‘black box’. Many of the projects I’ve undertaken I may never have even attempted had I been established in the field and thought I understood it well enough. When you switch questions, systems, or fields, there is a chance to really embrace your lack of understanding and not be scared to ask the most basic of questions — those that are often stated in the introduction of papers as fact, but do not actually have much empirical data behind them. When it was time to think about what I wanted to do for my postdoc, for example, I read all of the bacteria–phage literature that I could get my hands on. I found it all incredibly exciting, but was also frustrated that we had such a good understanding of what was happening and what could happen in a test tube, and yet so little understanding of what was happening and could happen in an actual population/community. That meant that I could start a project on what phages are doing in nature without the fear that it wouldn’t work, or the concern that I may not ever be able to unravel the complexity of the natural community. I felt we had a good enough understanding of what was happening at the mechanistic level — based on in vitro studies — that I could afford to test whether these led to the predicted general patterns in nature without too much focus on mechanism. Taking this approach allowed me to confirm some existing theoretical predictions about bacteria–phage interactions, and also to identify some intriguing and unexpected patterns (e.g. Koskella and Parr (2015) Philos. Trans. R. Soc. B 370, 20140297) that we are now working to explain using our laboratory model system. A lot of the research you’ve done could have been performed a hundred years earlier. Why do you think that it wasn’t? There is a lot of value in technological advancement (indeed, I have recently bought a droplet digital PCR machine for the lab and am amazed at what we can do and how quickly we can do it), but the research I’ve undertaken thus far has been much more driven by advances in scientific theory than advances in technology. As such, even though the methods I’ve used have been around for decades, the questions I am answering have not. I believe scientific advancement is in equal parts conceptual advancement and technological advancement, and that true progress requires investment — intellectual and monetary — in both. What is the best career advice you have been given? To remember that science is a long game. This was advice given by Professor Angela McLean from Oxford University during a talk she gave at an Athena Swan Women in Science event at the University of Exeter, and it has become my main mantra. With two young children and a husband who is also an academic, I find it very difficult to know when to say ‘yes’ and when to say ‘no’ to opportunities and requests. I am continually honored and humbled by the invitations I receive to speak, contribute to special issues, review papers and grants, and participate in various events — and, of course, engaging in such activities is key to success in my field. However, I also value my family life and love being at home with my kids. Turning down an opportunity is always a challenge, and I am now finding the need to do this much more often. I try to keep in mind that these opportunities are likely not specific to this particular time in my career/life. In other words, I don’t need to do everything now. And, as McLean rightly pointed out, a good supervisor/chair/dean will understand that your career is a long game and should be judged as such. What recent paper do you most wish you had written? There have been so many terrific new papers in the microbiome field that this is a very tricky question to answer. Instead, I will focus on the phage side of things and choose the paper by Erez and colleagues entitled “Communication between viruses guides lysis–lysogeny decisions”, which was published in Nature this year (Nature 541, 488–493). The idea that viruses can communicate with one another to influence decisions about life history is a total game changer. The question of when and how phages are selected to become lysogens (entering the host genome) or to lyse their host cells (thereby pumping out new virions that infect other cells) is one that has intrigued me since I entered the field. This is not just interesting in terms of evolutionary theory, but is critical in terms of predicting phage-mediated horizontal gene transfer, pathogen virulence, and impacts upon bacterial populations and communities. Their study shows that phages from one point in time can leave behind clues regarding host availability that influence the likelihood of ‘future’ phage integration into host genomes. The study is both elegant and intuitive, and I am excited to see how this result impacts upon the virology field as a whole. That brings up the question: are viruses alive? I will politely dodge that question by saying: they are not dead. If you were sitting next to a politician, what is the one point you would most like to convey about science? I believe very strongly in the importance of funding basic research. I think the link between basic research and applied ‘breakthroughs’ is often lost in translation from peer-reviewed science to popular media. As a result, there is a common misconception regarding how scientific funding can be most efficiently used to address societal problems. With few exceptions, funding aimed directly at solving a particular problem (e.g. how to edit a genome, increase crop yield, reduce antibiotic resistance, or cure a particular disease) does not lead directly to answers. Instead, most pivotal research that opens new research avenues for application has come from studying questions that are not obviously of applied relevance. I think this is a key point to emphasize, especially in the current political climate where scientific funding for human health is being increased, which is a good thing, but funding for more basic research (e.g. through the US National Science Foundation) is under constant threat. More generally, I would also work to emphasize the importance of teaching the scientific method and critical thinking. By making the scientific curriculum a key aspect of the K–12 experience, and getting students engaged in and excited about the process of science, the generation of data, and the ability to critically assess evidence, we will create a generation of citizens that are driven by, not weary of, data and empirically driven policy decisions. You seem to be quite active on Twitter. Do you think this is a good use of your time? Yes! Although I was never one to actively engage in social media before Twitter, I have found this particular platform (and community) to be a hugely valuable resource. In fact, when asked to do this Q & A, I turned to Twitter to ask for inspiration for questions to answer. Among the ways in which I find Twitter useful are: as a way to stay up-to-date with relevant literature; as a way of building a broad support network to both celebrate successes and commiserate about the many rejections encountered along the way; to highlight work that we are doing (if you haven’t read this paper, case in point here: Peoples et al. (2016) PLoS One 11, e0166570 — thanks @ScienceisMetal for alerting me to this); and to meet new collaborators and colleagues. I recommend Twitter regardless of whether you want to join the conversation — and there are a lot of terrific scientific debates on there — or just eavesdrop. Twitter has also allowed individuals who are united by experience, but likely will never meet in person, to come together and share ideas or empower one another. It also acts as a great stress relief at the end (or middle) of a long day. Drop in and say hello @bkoskella. If you would not have made it as a scientist, what would you have become? To be honest, I am still not sure if I’ve “made it as a scientist” and am always considering what I would do if I had to choose another trajectory. (And yes, I suffer from imposter syndrome, but have learned to embrace it rather than let it undercut my accomplishments.) Prior to entering graduate school, I would have loved to continue as a snowboard instructor. It was by far the best job I’ve ever had. With my given training now, however, if I had to leave Science I would most like to have a career as a scientific consultant whose main task was to help others identify the best experimental design to address a particular question. As far as I know, no such position exists, but it sounds like a little slice of science heaven to me. What do you think are the biggest unanswered questions in your field at the moment? As a bit of shameless self-promotion, I will point readers to our recent review of what theory still needs to be developed (or refined) to move the microbiome field forward (Koskella et al. (2017) Nat. Ecol. Evol. https://doi.org/10.1038/S41559-017-0340-2). I feel that the microbiome field is opening up more fundamental questions daily than I can even keep up with. Furthermore, the fields of ecology and evolution are both being challenged by the addition of a new axis: a rapidly changing climate. Predicting if, when, and how species and species interactions are being impacted by changes in land use, local climactic conditions, and human-mediated movement is key to understanding, for example, the spread of disease, the success or demise of particular species, and ecosystem stability. As we continue into the ‘Anthropocene’, we must acknowledge that much of what we have been working so hard to understand is already being rewritten. Finally, I think it’s important to consider the current unanswered questions regarding ethical considerations that have come to light given advances in both genome editing to alter individuals and ‘gene drive’ approaches to alter populations. As scientists, I believe we must be actively engaged in how science is used, and this can most readily be achieved through better public engagement and discourse.