Hard to even know where to begin, but the longer I have delayed the bigger the task… In the past almost four years there have been 27 papers that have come out. Way to go team! I will thus skip mentioning all of them (see publications for all of them), but here are some highlights:
- Former grad student Nick Leiby (now Lead Data Scientist at Kyruus) published a paper describing that metabolic tradeoffs in the Lenski long-term lines primarily arose due to mutation accumulation, rather than antagonistic pleiotropy (Leiby and Marx, 2014. PLoS Biology). This differed from earlier work from Vaughn Cooper and Rich Lenski, and the difference ended up being in the fact that Biolog plates commonly report upon non-growth associated metabolism, and thus are not necessarily a good fitness proxy. Vaughn (now at Pitt) wrote a really classy Primer to our paper about this (Cooper, 2014. PLoS Biology).
- Two former grad students, David Chou (now faculty at Taiwan National University and a father of two) and Nigel Delaney (now a Vice President at GenePeeks and a new father), and collaborator Jeremy Draghi (now faculty at Brooklyn College and also a new father) put together one of my personal favorite papers that showed that epistatic interactions between mutations can be predicted from their individual effects due to the combined effects of catalysis, enzyme costs, and toxicity (Chou et al., 2014. PLoS Genetics). This built upon the classic work from the mid- to late-80s of Tony Dean, Dan Dykhuizen, and Dan Hartl that inspired me to move toward systems biology in the first place.
- We enjoyed contributing to a collaboration led by Dom Schneider at Grenoble that exposed the role of epistasis in an adaptive radiation (Plucain et al., 2014. Science).
- Former postdoc Will Harcombe (now faculty at University of Minnesota) led our contribution to an awesome collaboration with Daniel Segrè‘s lab at Boston University that used flux balance analysis and the concept that individual species in a mixed community can be approximated as behaving according to their own metabolic optimum to predict community dynamics (*Harcombe, *Riehl et al., 2014. Cell Reports; software developed is called COMETS).
- Former postdoc Josh Michener (now Wigner Fellow at Oak Ridge National Laboratory) led a paper – with excellent collaborators Stéphane Vuilleumier and Françoise Bringel from Strasbourg – showing that evolving dichloromethane use across different species of Methylobacterium always involved increasing the ability to export the chloride ions, and in the process led us to identify the beneficial mutations in M. extorquens DM4 that occurred in nature to have evolved this capacity in the first place (Michener et al., 2014. eLife).
- We enjoyed contributing to a collaboration led by Mike Springer at Harvard Medical School that showed yeast respond to the ratio of galactose and glucose (Escalante-Chong et al., 2015. PNAS).
- Former postdoc Sean Carroll (now Senior Scientist at Axcella) led a paper (Carroll et al., 2015. Microorganisms) uncovering the genetic basis of adaptation for strains evolved to grow on methanol with a foreign metabolic pathway, work that began during my own postdoc with Rich Lenski, and first published by David Chou (Chou et al., 2011. Science).
- Former postdoc Deepa Agashe (now INSPIRE Faculty Fellow at National Centre for Biological Sciences, Bangalore), her team there, N. Ceci Martinez-Gomez (now faculty at Michigan State), and our group demonstrated that adaptation to suboptimal codon usage can involve single, large-effect synonymous mutations (Agashe et al., 2016. Molecular Biology and Evolution).
- Former grad student Dipti Nayak (now LSRF Simons Foundation Fellow at University of Illinois) led a paper showing why tradeoffs in using methylamine for a carbon or a nitrogen source explains maintenance of apparent metabolic degeneracy (Nayak et al., 2016. Current Biology).
- Former grad student Sarah Douglas (now Life Science Consultant at Simon-Kucher and Partners) got both of her papers from her thesis out that, together with Will Harcombe, Lon Chubiz, and my colleague Mary Ytreberg (here at Idaho) showed the genetic basis of the in-lab evolution of between-species cooperation of a pair of species (Douglas et al., 2016. PLoS One; Douglas et al., 2017. PLoS One).
- Former postdoc Alex Bradley (now faculty at Washington University, St. Louis) and former lab manager Paige Swanson (now Director of Research Operations at Finch Therapeutics Group) led a paper showing that elimination of hopanoid production in Methylobacterium leads to overproduced carotenoids and widespread growth impairment (*Bradley, *Swanson, et al., 2017. PLoS One).
- Former postdoc Lon Chubiz (now faculty at University of Missouri, St. Louis, and yet another new father) led a paper showing that the metabolic specialist Shewanella oneidensis can evolve glucose use rapidly, but that it comes at a tradeoff for use of other substrates (Chubiz and Marx, 2017. J. Bacteriology).
- My colleague Sergey Stolyar (Research Associate Professor here at Idaho) and I have enjoyed our collaboration with Ankur Dalia and Jake McKinlay at Indiana University, which has already resulted in Ankur’s group leading a paper showing the remarkable power of natural transformation for synthetic biology in Vibrio natriegens (Dalia et al., 2017. ACS Synthetic Biology).
It would be hard for me to be more proud of how well people from my lab have done… Looking forward to future updates about the current lab, which besides Sergey Stolyar mentioned above, includes postdocs Jessica Lee, Tomislav Ticak, Jannell Bazurto, and Eric Bruger, BCB grad student Siavash Riazi, and UGs Alyssa Baugh, Caleb Renshaw, Leah Lambert, and Nick Renn.
…but not there yet. Thanks for your patience.
Update 2017-07-07: We’re now actually getting the website restarted and up-to-date to reflect current people, projects, and publications here at UI. Cheers.
Well, I guess the blog title says it all… I am thrilled to say that I have accepted a position in Biological Sciences at University of Idaho and will start there in January. In nine short weeks since I first heard from the chair a positive vote was sending things in a good direction and today, we’ve managed to visit Moscow, ID, prepare and sell our house here, and buy one out there. As for my family, the truck arrives this Saturday to get our stuff and we’ll be driving that way soon. As for the lab, it will remain here until August so that most postdocs, students, and my lab manager can finish by then, and I’ll be back in Cambridge a few times next year to see that happen. In the meantime, I’m excited to participate in a cluster hire in systems biology at Idaho that is occurring simultaneously in Math, Physics, and Stats. I’ll miss many great people here in the Boston area and have been very thankful for the opportunity to start my career here and contribute to OEB. And no matter where I am: go Sox.
The past month and a half have seen several pieces of good news:
1. Will Harcombe’s paper just came out in PLoS Computational Biology. We are both extremely relieved and proud to have gotten this out, as it represents the first direct test ever as to whether central metabolic fluxes actually evolve to become optimal, as proposed by flux balance analysis. The answer is yes and no; strains that were already close to the optimum (for yield) actually evolved to be slightly further away from optimal than their ancestor. On the other hand, sub-optimal strains evolved to be closer. As Will very nicely put it, “FBA can either predict how you are or what you’ll become, but not both”.
2. We’ve been on a roll with Faculty of 1000! Lon and Miki’s PLoS One paper on FREQ-Seq to quantify allele frequencies cheaply and easily was kindly recommended by Andreas Wagner and Kathleen Sprouffske. Furthermore, our full FREQ-Seq kit is now available from Addgene.com, and they kindly wrote us up in their Summer Hot Articles newsletter.
3. I was very honored to have been nominated for a Star Family Prize for Excellence in Advising Harvard College undergraduates.
4. Finally, we have said goodbye and well wishes to Alex Betts, who visited us as an Erasmus Mundus visiting Master’s student (now on his way to a Ph.D. program at Oxford), and have welcomed Tim Scott, an visiting undergraduate student from University of Florida who joins us for the summer.
Less than two weeks after the last post, there is more happy news to report.
1. Nigel Delaney
‘s PLoS One paper
came out yesterday that describes the end result of an extended effort to push Methylobacterium
culturing as far as possible. It reports a new optimized medium, new strain lacking cellulose synthesis that caused clumping, and conditions and methods for high-throuput, robotic culturing that takes advantage of our earlier JALA paper
describing software to run automated lab systems.
3. Best of all, I am so thrilled to pass on that my PhD advisor, Mary Lidstrom
, was just elected yesterday
to the National Academy of Sciences. What a tremendously well-deserved selection for an incredible person. If nothing else, I have done well in choosing stupendous mentors: undergraduate work with Penny Chisholm
, PhD with Mary, and then postdoctoral work with Rich Lenski
. And now all three are in the NAS!
The last two weeks have seen much good news. First, Sean’s PLoS Genetics paper came out which describes analyses of global gene expression that occurred immediately after metabolic engineering of formaldehyde metabolism in Methylobacterium (i.e., acclimation to the new pathway) and after eight populations evolved to grow on methanol using a new pathway (i.e., adaptation). Remarkably, although there were massive transcriptional changes that were highly parallel across the evolved populations, nearly all of these simply reversed the immediate perturbations caused by swapping out the methanopterin pathway for a glutathione one. Second, in addition to the other kind press Miki’s Genetics paper on clonal interference that I mentioned before, undergraduate Lauren Claus wrote a very nice piece about it for the Harvard Crimson. Third, I am very thrilled to pass on that my graduate advisor, Mary Lidstrom (U. Washington), was named the laureate for the 2013 Procter & Gamble Award in Applied and Environmental Microbiology by ASM. Extremely well-earned! Fourth, I am extremely excited to say that our lab’s own Will Harcombe has had a successful job search, ending in an excruciating decision. He will be starting off 2014 as an Assistant Professor in the BioTechnology Institute at the University of Minnesota as a member of the Department of Ecology, Evolution and Behavior.
With two weeks remaining in winter, the season about to end has been actually been pretty good to us with the exception of the record-breaking 28″ dump last month. I can start by congratulating Josh Michener for landing an NRSA postdoctoral fellowship (and for his PNAS paper that emerged from his graduate work with Christina Smolke). It has also been quite nice to see four more papers surface from the lab in the last two months. The first one came out in Molecular Biology and Evolution and describes work by my former postdoc, Deepa Agashe (now running her own lab at the National Centre for Biological Sciences in Bangalore, India), who looked at the selective pressures acting upon codon bias. She systematically varied codon throughout a highly-expressed methylotrophy gene in Methylobacterium extorquens AM1, generating seven synonymous variants to compare to the wild-type coding sequence. Remarkably, the selective effects we report were massive, including that the “perfect gene” comprised of exclusively the most frequently-used codons expressed very little protein and led to extremely low fitness. Thanks to our collaborators Allan Drummond (now at University of Chicago) and Ceci Martinez-Gomez (Lidstrom lab, U. Washington) for their great help. The second was a project from the lab of Chuck Davis (Harvard) in PLoS Genetics that I contributed to in terms of thinking about the parallels between horizontal gene transfer in bacteria and what they have observed between the mitochondrial DNA of a parasitic plant and its host. The third is a Primer I wrote for PLoS Biology that discusses just how much of ecology or evolution can be detected from metagenomic sequencing. A major goal of the paper was to frame an excellent paper in the same issue from Matt Herron and Michael Doebeli that examined adaptive diversification in a two resource environment. Finally, the fourth just came out today as a Highlighted Paper in this month’s issue of Genetics. This describes work by my former graduate student, Miki Lee (now a postdoc in the lab of Jiandong Huang at the University of Hong Kong). Early in her thesis she discovered that a surprising kind of beneficial mutation – the integration of an introduced plasmid into the host genome – occurred many times in each of eight evolving populations. During a five month post-defense mini-postdoc, one of the things she did (besides co-develop FREQ-Seq) was to follow-up on her old results and put together a fascinating story of clonal interference between simultaneous versions of this type of mutation (not to mention everything else going on). She detected waves of up to 17 similar (but distinguishable) alleles all rising and falling in the same population, only sometimes ( 3 of 8 ) being fortunate enough to give rise to the eventual winning lineage. Adaptation is not simple, but it is undoubtedly amazing in the outcome and the process.