Category Archives: publications

First test of FBA’s ability to predict evolution published; a third F1000 recommendation and Addgene.com article; mentoring nomination; lab comings and goings

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.

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New paper; another Faculty of 1000 recommendation; and Mary Lidstrom elected to the National Academy of Sciences

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.
2. Deepa Agashe‘s Molecular Biology & Evolution paper demonstrating tremendous selection upon codons was recommended in the Faculty of 1000 by Deborah Charlesworth.
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!

New PLoS Genetics paper; Harvard Crimson article; Mary Lidstrom wins Procter & Gamble Award; Will’s future job

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.

Praise for Miki’s paper; TV show; ASM Distinguished Lectureship

1. In the past three weeks we’ve been fortunate to have received some additional press for Miki’s recent paper mentioned in the prior post.  Beyond being a ‘Highlighted Paper‘ in the March issue of Genetics, we were kindly recommended by Deborah Charlesworth of the Faculty of 1000, and the Harvard Gazette ran an article about it, too.
2. Back on Darwin’s birthday (12 February) I went to the Belmont Media Center to feature in an episode of Contemporary Science Issues and Innovations on “Microbe Evolution.”  It was good fun talking about aspects of our work on the evolution of cooperation in multi-species microbial consortia, particularly given an enthusiastic of high school biology students (earning extra credit for attendance).
3. Finally, thanks to a very kind nomination by my PhD advisor, Mary Lidstrom, I was named an ASM Distinguished Lecturer for 2013-2015.  I am looking forward to the opportunity to speak at ASM Branches over the next couple years.

Latest News:

Remarkably, three more months have gone by since my last post.  We have crowned a new Ph.D. from the lab, Dr. Nigel Delaney, back on 30 October.  He gave a fantastic presentation concentrating on his new work estimating the distribution of fitness effects of successful mutations for one of our strains of Methylobacterium.  He has now gotten started at his new position at the Broad Institute working with Vamsi Mootha
We’ve also seen two new papers come out, both including Nigel, in fact.  The first of these describes ‘Clarity‘, an open-source program to manage lab automation that he worked on with Jose Rojas Echenique.  We’ve used this to run our automated, robotic growth analysis system, but it could be applied to any given automation challenge.
Second, we have published a paper describing ‘FREQ-Seq’, a new method to rapidly determine allele frequencies directly from mixed populations.  Developed by Lon Chubiz and Miki Lee, this is an efficient way to barcode samples and shine the light of Illumina sequencing on just known sites of interest, thereby generating phenomenal depth of coverage (~150,000x for 100 samples in 3% of a lane) and avoiding any typical Illumina library prep.  The bridging primers with barcodes for this can be regenerated from a panel of plasmids available through the non-profit plasmid distribution organization, Addgene.org.  Nigel developed a software program, ‘FREQout‘, that allows users to rapidly extract frequency information from the Illumina data.  We sent this to Yousif Shamoo’s lab for testing and they’ve completed all the data they needed for part of their paper in press at PNAS in the very first go.

End of Summer Update.

In the past month and a half we’ve had four new papers come out. First is one led by myself and Stephane Vuilleumier in Journal of Bacteriology announcing the genome sequences of six strains of Methylobacterium. Second, Hsuan-Chao Chiu, his then-mentor Daniel Segre and I have a follow-up to last year’s Science paper in Proceedings of the Royal Society B that extends some general theory that considers how epistasis arises from the dependence of fitness upon underlying traits. Third, David Robinson and Miki Lee (former undergrad and grad student, respectively) led a paper that came out in Nucleic Acids Research describing a new program (OASIS) for automated annotation of transposable elements from genome sequences and some surprising findings regarding their distribution. Finally, Nick Leiby and Will Harcombe worked to report in BMC Evolutionary Biology that a few of the Lenski long-term E. colipopulations have become dependent upon citrate for growth on glucose.

Comings and Goings, Grants, and Publications.

In the midst of a busy summer, we have had some comings, goings, new grant, and a new paper. We welcome Sherif Gerges as a visiting summer undergrad and Josh Michener as a new postdoc, fresh off his Caltech Ph.D. Unfortunately we had to give our best wishes to a few departing lab members: postdocs Jessi Purswani (headed back to Valencia for a postdoc) and Alex Bradley (starting off his new lab at Wash. U.), and lab manager/technician extraordinaire Maryska Kaczmarek (heading off to study Evolution for her Ph.D. at UT Austin). Speaking of UT Austin, a proposal led by Claus Wilke to the Army Research Office there has been awarded. His lab, ours, and six others are looking to see if we can make a statistical association between growth conditions and cellular composition. Should be a fun challenge! Finally, a new paper of mine has been accepted that describes an accidental, surprising finding of mine a few years ago. Some of the replicate populations I initiated didn’t grow to full density from single colonies that I used to start each one, and they started to crash. Most of them recovered after a few cycles but one population remained alive but >100 times lower density than the others. It turns out that it specifically adapted to life at low density and lost fitness at standard densities.