R. Keith Slotkin

Associate Professor
Faculty

Transposable elements are stretches of DNA that can duplicate or move from one location in the genome to another. Their ability to replicate has resulted in transposable elements occupying vast amounts of most eukaryotic genomes, including nearly half of the human genome. Although often overlooked or dismissed as “junk DNA”, transposable elements have played an important role in the structure and evolution of the eukaryotic genome.

When transposable elements are active, they cause DNA damage and new mutations by inserting into essential protein-coding genes or by promoting rearrangements and genome instability. To suppress the inherent mutagenic potential of transposable elements, over a billion years ago eukaryotes evolved a genome-wide surveillance system to target transposable elements for inactivation. This process of selective inactivation takes advantage of the transposable element’s propensity to generate double-stranded RNA, which is the trigger for small RNA-based silencing mechanisms. These silencing mechanisms result in either post-transcriptional silencing or chromatin modifications. One such heritable chromatin modification is DNA methylation, which can be propagated from cell to cell (through mitosis) or from parent to progeny (through meiosis and fertilization). This heritable repression of gene expression is referred to as epigenetic regulation, and is not the result of changes in the primary DNA sequence (ATGCs). Epigenetic changes are distinct from genetic changes because they are readily reversible, making them exceptional targets of short-term or generation-to-generation environmental modulation.

For more information on the epigenetic regulation of transposable elements, see Slotkin and Martienssen, 2007, Nature Reviews Genetics.

My laboratory uses Arabidopsis thaliana (thale cress), a reference flowering plant, as a model to investigate basic biological questions exploring how the eukaryotic genome and transposable elements interact over the development of a single generation, as well as across evolutionary time. Plants offer a unique opportunity to study transposable elements. Unlike animals, plants lack a germline that is set-aside early in embryonic development, meaning that epigenetic changes that occur during plant development are more likely to be transmitted to the next generation. Furthermore, mutations in the genes responsible for epigenetically suppressing transposable elements in plants are viable, while the corresponding mutations that similarly act to silence transposable elements in mammals are embryonic lethal.

 

Projects in the laboratory focus on the following:

  1. How the cell recognizes which regions of the genome are genes and should be expressed, and which are transposable elements and should be selectively silenced

  2. How epigenetic information targeting transposable elements for silencing is propagated from generation to generation, protecting each generation from new mutations

  3. How active transposable elements are initially triggered for silencing and how epigenetic modifications are first targeted.

  4. How the recruitment of epigenetic control to transposable elements has been co-opted over evolutionary time to produce novel and interesting examples of gene regulation.

 

Current Lab Members:

Lab Alumni:

  • Germán Martinez-Arias (Postdoc) is currently in the European return phase of his Marie-Currie Fellowship in the lab of Claudia Köhler at the Swedish University of Agricultural Sciences
  • Chris DeFraia (Postdoc) is currently an Assistant Professor at Ferris State University
  • Andrea McCue (Graduate Student) is currently a Postdoc at the NIH in the lab of Shiv Grewal
  • Saivageethi Nuthikattu (Graduate Student) is currently a Postdoc at the University of California Davis in the lab of Amparo Villablanca
  • Erica Thomas (Undergraduate Student) is currently in a PhD program at Washington University in St. Louis in the lab of Hani Zaher
  • Jennifer Bosse (Undergraduate Student) is currently in the MCDB Graduate program at The Ohio State University in the lab of Heithem El-Hodiri 
  • Jeff Kovach (Undergraduate Student) is currently studying plant biology in a PhD program at Michigan State University

 

 

Slotkin Lab Members
 
Slotkin Lab Members - 2015

 

Currently Teaching

  • MG5601 – Undergraduate level Eukaryotic Molecular Genetics Lab
  • MG5700 – Graduate level Systems of Genetic Analysis
  • Annual Biology Enhancement Workshop, taught to 7th grade students in conjunction with the Ohio State Young Scholars Program

 

Publications:

 

Grants, Fellowships and Awards

Areas of Expertise
  • Epigenetics, Transposable Elements, Small RNAs
Education
  • PhD – The University of California Berkeley (2000-2005)
  • Post-Doctoral Research – Cold Spring Harbor Laboratory (2005-2009)
  • Bachelor of Science - The University of Arizona (1996-2000)
R. Keith Slotkin
Phone:
614-292-1087
Fax:
614-292-6345
570 Aronoff Laboratory
318 West 12th Avenue
Columbus, OH 43210