- University of Utah
- Department of Human Genetics
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- Bioscience PhD Program Profile
The Feschotte Lab
Eccles Institute of Human Genetics
15 North 2030 East
Salt Lake City, UT 84112
Office: Rm. 6150
Office: (801) 585-6061
Alesia awarded Damon Runyon Postdoc Fellowship!
KUDOS to Alesia McKeown who was awarded a prestigious 4-yr postdoc fellowship from the Damon Runyon Cancer Research Foundation.
The fellowship will support her innovative work on retrogenes as viral restriction factors, in co-sponsorship with Nels Elde.
ERV colonizes bat, cat, and... uh pangolin
Very proud of Xiaoyu Zhuo's new paper (second chapter of his dissertation) just out at PLOS Pathogens.
In this study, Xiaoyu provides compelling evidence for the cross-species transmission of an endogenous retrovirus across three orders of mammals: vesper bats, felid cats, and pangolin.
The biggest surprise however is that, despite being derived from the same viral species, the ERV experienced very different amplification dynamics in the three mammalian lineages. Notably it seemed to have remained infectious for extended period of time in bats and may be still infectious today. Scary, eh?
To find out how the story ends, read the paper here.
Human transposase-derived PGBD5 is an active recombinase!
The lab has long been intrigued by genes that have emerged from transposons. Perhaps the most spectacular example of a domesticated transposon gene is RAG1, the recombinase that enables the diversification of antibodies in our immune cells.
There are dozens of other genes derived from transposon proteins in the human genome. We can tell they encode proteins with cellular function (they have evolved under strong purifying selection) but for most we have no idea what the function is. Could they be another active recombinase like RAG1 diversifying our somatic genome?
One interesting candidate we've been working on for some time is PGBD5 - it's derived from a full-length transposase of the piggyBac family and it's extremely conserved across vertebrates. Alan Weiner's group showed a couple of years ago PGBD5 is >500 My old, even older than RAG1. Intriguingly, in humans and mice, PGBD5 is expressed predominantly in the cortex. But PGBD5 function is a complete mystery.
Alex Kentsis' group at Memorial Sloan-Kettering has taken a major step toward understanding PGBD5 function. In a paper just published in eLIFE, Anton Henssen et al. show that the human PGBD5 protein has retained catalytic recombinase activity. It can do the cutting-and-pasting business of a transposase.
The conservation of DNA transposition activity by PGBD5 after >500 My of domestication suggests that its catalytic activity is important for cellular function. We speculate that PGBD5 promotes some type of genomic remodeling in the brain... let's see if we can prove it.
Tommy Carter, PhD student, is the newest addition to the lab!
Tommy Carter graduated Summa Cum Laude from CU Boulder where he worked in Brad Olwin's lab developing a hydrogel culture system to promote satellite cell selfrenewal in vitro. During his undergrad project, Tommy also developed a techinique for isolating primary Sdc4+ satellite cells using magnetic dynabeads. His undergraduate honors thesis can be found here.
Currently, Tommy is investigating the impact of transposable elements in the birth and evolution of lncRNAs.
In his free time, Tommy enjoys scuba diving crossfit, playing fetch with his cat, growing his beard out for the winter.
Opening Pandora's Box (and unleashing Submariner)
This is a typical mariner DNA transposon family that has spread to 30 copies in the viral genome and is similar to a mariner transposon from the alleged Pandoravirus host, Acanthamoeba - suggesting Pandoravirus acquired it from a eukaryotic host. As often, my contribution to the actual work was minimal, largely limited to the branding of the element as 'submariner'.
This discovery continues to blur the division between viral and cellular genomes and highlights the remarkable promiscuity of mariner transposons.
The paper, published in BMC Biology, is here.
Greetings to Alesia McKeown, a new postdoctoral associate jointly working with Nels Elde.
Alesia obtained her PhD from the University of Oregon where she worked with Joe Thornton (now at Chicago). Her research elegantly combined biochemistry, biophysics phylogenetics, and ancestral protein reconstruction to delineate the molecular evolution of DNA binding specificity in the steroid receptor family of transcription factors (read her fantastic Cell paper).
In her current project Alesia is studying the evolution and function of novel antiviral proteins.
As an outdoor enthusiast, Alesia is fully enjoying Utah's natural playground as the pic above can attest!
Fight Fire with Fire: ERV Envelope genes as antivirals
In this 'Gem' article in the Journal of Virology, Ray and I discuss the mechanism by which some envelope genes derived from endogenous retroviruses offer host cells protection against exogenous retroviral infection. We argue that many more envelope-derived restriction factors await discovery in vertebrate genomes, including the human genome.
The paper is available here in Open Access.
Transposons catalyzed the evolution of pregnancy
Ed talks at CSHL meeting in Puerto Rico
Ed has promised to stay away from Pina Colada until he delivers his talk 'Endogenous retroviruses facilitate the evolution of gene regulatory networks encoding immune defenses' [collaborative work with Nels Elde].
Danger danger! Volatile evolution of lncRNAs!
Ray awarded F32-NRSA NRNIH postdoc fellowship
Congrats to Ray for being awarded a prestigious F32/NRSA grant from NIH/NIAID to work on cellular genes born from endogenous retroviruses.
[True that bottle of TBE looks yum but let's go for champagne this time]
Cedric is now on Twitter...
Also be warned: views expressed here are solely my own.
piRNAs, lncRNAs and mobile DNA
We collaborated with Jin Xing and Kevin Chen at Rutgers to shed light on the intricate relationship between human piRNAs, lncRNAs, and mobile elements.
Paper is here.
Image: human testis uncensored [credits]
Ed becomes Fellow of Jane Coffin Childs Fund!
Congratulations Ed for landing a 3-year postdoctoral fellowship from the prestigious Jane Coffin Childs Memorial Fund for Medical Research.
To top the cake off, Ed was designated as one of eight HHMI Fellow of this year's JCC Memorial Fund.
Ed's project on ERVs in innate immunity is co-sponsored by Feschotte and Elde.