Dr. Jack Gilbert, a microbial ecologist with academic appointments at The Microbiome Center, The University of Chicago, The Marine Biological Laboratory and Argonne National Laboratory, will be giving a keynote address at the upcoming 3rd Annual Translational Microbiome Conference organized by Arrowhead. We recently chatted with him about his work and how next gen sequencing is having an impact.
AllSeq: Your bio lists four different current job titles, which sounds like you might be a busy man. Can you give us a little background on what you do and how you balance these roles?
Dr. Gilbert: Balancing any role is hard, I just view what I do to require a multidisciplinary approach and extensive collaboration. Microbes are everywhere and as a result I feel compelled to follow exciting science wherever it leads me. This means that despite being trained as an entomologist and then as a microbial ecologist in water and soil, I have ended up with my primary appointment being a Professor of Surgery. But while I am interested in human health, I also believe that we need to understand the planet, and to invoke the idea of ‘one health’, whereby our wellbeing is intrinsically linked to the wellbeing of our world. I maintain appointments in places that enable me to pursue my research interests, and while this means that I feel like I am constantly moving it does keep me entertained. I love working with brilliant people as well, and the institutes I affiliate with have brilliant people working in them, and that is a real incentive to deepen ties and interactions.
AllSeq: From a sequencing technology standpoint, microbiome studies seem especially challenging as they would benefit from both longer reads AND more reads, as well as posing significant data analysis difficulties. What do you think the biggest challenges are?
Dr. Gilbert: The biggest challenges actually revolve around balancing the experimental design with the tools available to us. I know I am in a privileged situation, at Argonne and UChicago I am anything but compute limited; but I really feel that the tools available for data analysis are out there and constantly being improved, what is important is matching our hypotheses to the tools available. So not just sequencing for sequencing sake, but ensuring that we blend our capabilities across many platforms. Importantly, we tend to employ amplicon sequencing to screen samples and find trends, shotgun metagenomics and metatranscriptomics to explore the functionality of these communities, and define specific genomes and how they are responding to the system, and to build metabolic models of their interactions, and then metabolomics to validate our predictions and build out new knowledge on how metabolic networks function. The biggest challenge is therefore the efficient and routine integration of these data, and then sharing of that data. We all need to be better stewards of our data resources, and this means building new data commons and standards that help with sharing and analysis.
AllSeq: What improvements in NGS are you looking for?
Dr. Gilbert: Longer reads always help, and obviously the cheaper the data generation the bigger our questions can be. But to be honest, what I am most looking for is the capacity to reduce the input material required – heading into the sub nano gram level, with reliability and sequencing fidelity. I am excited by the options available with nanopore and other single molecule platforms, and while we use these in single isolate genome sequencing, I am waiting for further improvements before replacing our standard platforms.
AllSeq: Can you tell us a little about how Microbiome-Wide Association Studies work (especially as they contrast with GWAS)?
Dr. Gilbert: GWAS obviously focusing on the genome, whereas MWAS focuses on the microbiome, and by that I mean the microbial community composition, structure AND function. We engage in metabolomics, metagenomics, metatranscriptomics and how these components interact with ‘predominantly’ host-associated systems. In a way MWAS is a mechanism of biomarker discovery and hypothesis generation, but it can also be used to help form the groundwork for some pretty awesome metabolic modeling systems, that can tell us more about how these systems function than annotation and observation of data structures alone.
AllSeq: What are your thoughts on the ‘direct to consumer’ microbiome space?
Dr. Gilbert: Right now I am skeptical about my own abilities to diagnose disease from the microbiome per se. However, I know we can use the microbiome to influence disease onset and progression for specific diseases states, and I do not think we are far off having the power in our data to generate some predictive modeling systems that will allow us to determine whether a patient will respond to a particular drug therapy or surgical intervention. Of course we need to be careful to ensure that we don’t rely on the microbiome alone, we need to leverage all data streams at our disposal. But the power of these approaches and data resources, still lies firmly in the clinical practice. I can sequence my microbiome at will, and yet even I would be hard pressed to determine exactly what is wrong with me.
AllSeq: Finally, you’ve got a very strong following on Twitter. Is this primarily a way for you to interact with your colleagues, or is it a way for you to reach a broader, non-expert audience?
Dr. Gilbert: I interact with my colleagues and with the public by making myself available, by always listening, and by respecting others no matter at what level of society, education or self-expectation. I am always respectful but irreverent, and continually challenge people to apply critical thinking to everything that they observe and explore. Social media (Twitter, Facebook, Snapchat, even LinkedIN) are very valuable for allowing me to reach out and understand the complex knowledge streams that are out there, and they have led to collaborations in the past. But primarily I find it is a great way to advertise new work, whether it is published in my journal mSystems, or the work from my lab colleagues, I really see these streams as helping to restrict the firehose so that I can get a better feel on the latest work in the field, and hopefully help others to do the same.
Be sure to catch Dr. Gilbert’s presentation at the 3rd Annual Translational Microbiome Conference, this April 11th – 13th in Boston, MA. Use the code ‘ALLSEQ’ for a 15% discount off registration!