Author Archives: cmarx2014

New paper describing the formaldehyde sensor EfgA is out in PLOS Biology, and two more from Jannell Bazurto expanding upon its role

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.

New paper on synthetic communities by Jessica Lee

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.

Deepa Agashe wins a national award from the Indian President

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.

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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.

Dipti Nayak named a Searle Scholar!

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!

The presentation that wasn’t…

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.

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Purely “Lamarckian” evolution?

Yup, I really wrote that.  In a lab so strongly influenced by Darwin, I just invoked the name of Lamarck, who is often framed as the anti-Darwin. In no way am I defending any aspect of Lamarck’s support of the “Great chain of being” to describe the
(super)natural progression of organisms through time. Rather, I am invoking the evolution based upon acquired phenotypes. This has been rightly dismissed as being able to describe any broad timescale of evolution, but what about the potential role for epigenetics? Might anything here be considered evolution?

Late in 2019, a paper from our lab championed by Jessica Lee and co-first author Siavash Riazi describes how Jessica discovered that phenotypic variation can permit a population  of Methylobacterium extorquens to survive an otherwise lethal formaldehyde stress (PLOS Genetics, 2019. 15:e1008458).

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Jessica found that the rare survivors were phenotypic variants (no mutations anywhere), supported by several methods including excellent video microscopy data (below) from Shahla Nemati in the lab of Andreas Vasdekis here at University of Idaho (who recently was promoted to Associate Professor in Physics, woo hoo!). Rather than having a population of discrete populations of highly tolerant and weakly tolerant cells (akin to antibiotic persistence), Jessica found that the concentration that cells could survive was a wide, dynamic continuum.Screen Shot 2020-04-10 at 5.02.46 PM.png

Siavash led our effort to model how this distribution of tolerance changes in different environments in terms of growth, death, and transitioning across a continuous scale of formaldehyde tolerance. Working with co-advisor Chris Remien, Ben Ridenhour, Jessica, and myself, he was able to develop a simple PDE that allows us to conclude, amongst other things, that formaldehyde tolerance is inherited over a large number of generations. Finally, Jessica and Jannell Bazurto analyzed RNA-Seq data to determine that these phenotypically tolerant cells have a distinct transcriptome from either low tolerant cells or the immediate stress response of low tolerance cells to formaldehyde exposure.

All told, we observe selection upon phenotypes that show a fair amount of phenotypic inheritance: all the ingredients that define evolution. No allele changes were observed, but the distribution of inherited phenotypes did change. As a visual metaphor, I discussed this scenario with visual artist Cody Muir, who was at IBEST, and this resulted in a fun visual that mixes seeing only some colonies grow with the Lamarckian metaphor of the giraffe’s neck:

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Moving forward, we look forward to uncovering the physiological basis of phenotypic heterogeneity/inheritance, as well as beginning to look at how Lamarckian and Darwinian processes can jointly influence evolutionary outcomes.