Keith’s research is focused on elucidating the mechanisms plant cells use to identify, target and repress genome parasites. Without a brain or nervous system, plants can sense subtle changes in the environment and direct the appropriate response. This response is dictated at the cellular level, as each cell alters which genes are active vs. repressed to produce the appropriate whole-organism response. Similarly, each plant cell has an innate ability to understand which parts of their DNA are safe for them to activate (the genes), and which regions are not safe and should not be activated. For twenty years Keith’s research has focused on the regions of plant genomes that are dangerous when activated, known as ‘jumping genes’ or transposable elements. These regions of the genome are often thought of as tiny parasites, as their activity leads to DNA breaks and new mutations that are harmful to the cells. Although harmful to the cells on the scale of a single lifetime, over long evolutionary timescales transposable elements generate the raw mutations and rearrangements necessary for the production of new traits by natural or artificial selection.
On the single generation time scale that can be investigated in the laboratory, the plant spends considerable energy to identify transposable elements within its genome, target them for repression (so they do not activate, jump, and create new mutations), and then maintain that repression across cell divisions and from generation to generation. The Slotkin laboratory’s goal is to determine how plants identify which regions of their genomes are transposable elements. Multiple projects in the Slotkin laboratory focus on understanding the basic mechanisms that the cell evolved to decipher what is a gene vs. what is a transposable element, and the proteins and small RNA molecules the cell uses to specifically target transposable elements for repression. To dissect these processes, the Slotkin laboratory divides the distinct stages of repression into: initiation, establishment and maintenance of transposable element silencing.
The Slotkin laboratory does not focus on any one transposable element out of the tens of thousands in a plant genome, but rather uses a combination of whole-genome bioinformatics to identify large trends and then design specific laboratory ‘bench’ experiments to scientifically test and potentially prove their discovery. The Slotkin laboratory has found that the key to repression is the degradation of transposable element RNA transcripts into small RNAs, which then act as sequence-specific guides for protein silencing complexes. The overarching themes of the Slotkin laboratory’s discoveries over the past five years have demonstrated that plant cells will use any of their myriad of multiple small RNA pathways to trigger transposable element repression, and that these small RNAs are passed to the gametes to ensure transposable elements remain repressed.
Understanding how transposable elements are regulated is the specific focus of the Slotkin laboratory, but the impact of their research extends beyond transposable element biology. Plant cells use the same mechanisms to defend themselves against transposable elements, viruses and some pathogens. Understanding how transposable elements are targeted for repression has also led to the production of enabling technologies that target gene repression or make genes resistant to repression. The Slotkin laboratory’s long-term goal is to produce the necessary basic understanding required to empower new and better tools that facilitate plant trait development towards humanity’s improved use of the environment.