Congrats to Eric Bruger and his coauthors for his new paper in Genome Biology and Evolution that built upon our old work on epistatic interactions between beneficial mutations (Chou et al., 2011. Science) to show that beneficial mutations can also be key in how new pathways work together.
Most prior work has looked at beneficial mutations, but not necessarily combined with gene loss and gene gain events. In terms of understanding how organisms can evolve to have multiple, degenerate (analogous functions with unrelated parts) pathways, it is critical to consider all types of genetic events that can occur. Eric found that the utilization of a foreign pathway for formaldehyde oxidation was deleterious in the presence of the native pathway, unless there were also some beneficial mutations present that help put the foreign pathway to good use. This indicates that even if degeneracy is initially disfavored, and the dual pathway scenario is initially disfavor able (red and orange arrows below) there may be one or few steps needed for it to be stabilized and have multiple pathways be beneficial (the dark blue arrow below).
After a long period of work and many contributions from collaborators and many people within the lab our discovery of the formaldehyde sensor EfgA came out in a paper in PLOS Biology. This work, led by Jannell Bazurto (now faculty at University of Minnesota) and initiated by Dipti Nayak (now faculty at UC Berkeley) describes the surprising finding that methylotrophs possess a sensor for formaldehyde that appears to directly lead to growth cessation if levels of the potent toxin rise too high.
Collaboration with Yousif Shamoo at Rice University led to solving the crystal structure of EfgA and the formaldehyde binding pocket, a result supported by both computational work by Jagdish Patel and Marty Ytreberg here at University of Idaho, and biochemical experiments by a former postdoc, Tomislav Ticak, who is now a Scientist at Proctor & Gamble). Rather unexpectedly, introduction of EfgA from Methylorubrum extorquens into Escherichia coli resulted in an enhanced ability to grow on glucose in the presence of formaldehyde. This result, as well finding alternative loci for beneficial mutations that enabled growth on formaldehyde has led to the working model that EfgA binds formaldehyde and directly interacts with ribosomes to slow or shut down translation in response to elevated internal formaldehyde.
Two other recent papers by Jannell build upon this result. First, a paper in Journal of Bacteriology demonstrates that EfgA (as well as the MarR-like transcriptional regulator we name TtmR) is critical for the transition from multi-C substrates to C1 substrates like methanol. Second, a paper co-first authored by former PhD student Siavash Riazi and in collaboration with Jeff Barrick at UT Austin in Microorganisms shows that the global transcriptional response of cells to formaldehyde bears many similarities to exposure to a translational inhibitor (kanamycin).
All of this goes to show that methylotrophs possess more than just the enzymes to convert C1 substrates into energy and central metabolites, but that they also possess an intricate system of regulators that appear to work at both transcriptional and translational levels to deal with the toxicity encountered dealing with formaldehyde as a central metabolite.
Finally, there are a couple nice press releases put out by Rice and PLOS (on EurekaAlert, AAAS) on this work. Thanks so much for these.
A paper in Microorganisms by former postdoc, Jessica Lee, now a scientist at NASA Ames Research Center, came out earlier this year describing her development of a synthetic community that could degrade model plant-derived compounds. She uncovered myriad metabolic interactions that arose, including formaldehyde toxicity from vanillic acid conversion that poisoned one community member but could be mitigated by inclusion of Methylorubrum extorquens PA1.
I am thrilled to say that another former postdoc, Lon Chubiz, will become a tenured Associate Professor in the Biology Department at University of Missouri, St. Louis, as of Fall, 2021. After having also landed an NSF CAREER Award, way to kick butt, Lon!
I just realized that I never posted the great news from last year that Josh Michener, a former postdoc, won a DOE Early Career Award. This supports his lab’s work at ORNL on “Systems Metabolic Engineering of Novosphingobium aromaticivorans for Lignin Valorization.” Congratulations on the distinction, as well as five years of funding!
Shout out to former postdoc, Will Harcombe, on bring promoted to Associate Professor this past summer. Very exciting to see how well things have gone with his lab’s exploration of the evolution of cooperation.
Deepa Agashe, at NCBS in Bangalore, has been awarded one of three “SERB Women Excellence” Awards and was recognized directly by the president. Not that president, but the Indian President, Shri Ram Nath Kovind. As they call out on their website:
Dr Deepa Agashe is a biologist, working at the interface of evolutionary biology, ecology, and molecular biology. Using diverse tools such as experimental evolution, genomics, molecular analyses and phylogenetics, she aims to understand how bacteria and insects adapt to new environments. Dr. Agashe received her Bachelor’s degree in Microbiology from Abasaheb Garware College (University of Pune) in 2003, followed by a PhD from the University of Texas at Austin, the USA in 2009. Her thesis work showed that genetic diversity could stabilize animal populations and facilitate adaptation to new niches. During her postdoctoral work at Harvard University, USA, she proved that so-called “silent” mutations could have enormous effects on bacterial evolution. In 2012, she returned to India to lead a research group at the National Centre for Biological Sciences (NCBS–TIFR), where her team is dedicated to unravelling the causes and mechanisms of evolution.
Way to go Deepa! Yet another lab alum making us all proud.
Deepa and me during a jeep safari through the Biligirirangan Hills, which was a lovely break after she had invited me to be an instructor at the ICTS 4th Bangalore School of Population Genetics and Evolution that she co-led this past April.
Congrats to Dipti Nayak, who is still in her first year of being an Assistant Professor in Molecular and Cellular Biology at UC Berkeley, on being named one of the 15 Searle Scholars for 2020. She was honored due to exploring “how do archaea produce and consume the greenhouse gas methane, and how can they be engineered to address environmental and biotechnological challenges.” You make us all proud, Dipti!
Remember March 1st of this year? Kids were in school and labs were open. As for me, I was about to get on a plane to fly from Copenhagen through to Denver for the American Physical Society (APS) general meeting to give a talk. With less than 24 hours to go before the meeting began the whole >10K person meeting was cancelled. This was, of course, just the beginning of many changes that were to come.
APS has decided to open up the ability for presenters to post slides of their talks and I have gone ahead and put my slides up online. This is basically the abbreviated version of Jessica and Siavash’s paper that I mentioned below. I was sorry to miss the opportunity to see people there, but I look forward to attending to present in the same session next year in Nashville. Let’s hope that, by then, social distancing will be a distant memory from the past.