Dr. Chris Nelson

 

Research of Dr. Chris Nelson
PhD UBC

Eukaryotic cells use histone proteins to package their DNA into nucleosomes, which are the fundamental subunits of chromatin. The assembly of nucleosomes into higher-order states facilitates a remarkable compaction of DNA but restricts access to the genetic template. For example, enzymes that participate in transcription must overcome the barrier of chromatin to interact with the promoter and coding regions of a gene. To contend with the obstacle that nucleosomes and higher-ordered chromatin present, eukaryotes use enzymes to dynamically modulate the properties of the chromatin fiber.

nucleosomes

The Nelson lab employs Sacchromyces cerevisiae, or budding yeast, as well as cultured human cells to identify, dissect, and understand how chromatin regulatory pathways control the process of transcription. Currently, our research focus is a unique enzyme family: peptidyl-proline isomerases (PPIs).

PPIs modify the fold of proteins by catalyzing the cis - trans isomerisation of proline-containing peptide bonds in proteins. Since the geometry of cis and trans proline is dramatically different, proline isomerisation has the potential to alter the structure and function of proteins.

cis-, trans-proline

We have shown that proline isomerisation of histones is a novel type of chromatin modification which regulates transcription. Aims of the lab include understanding the molecular details of how histone proline isomerisation alters the structure and function of histones, nucleosomes, and the chromatin fiber. We are also defining how PPI enzymes modulate additional processes including transcription and signal transduction. We employ molecular biology, biochemistry and genetic techniques to address these aims in yeast. In human cells we complement classical biochemical assays with powerful genomic and proteomic approaches to characterise PPI enzymes.

Failure to establish appropriate chromatin environments can result in loss of gene regulation. Accordingly, enzymes that modify histones are frequently mutated in a variety of diseases, including cancers. Our long-term objective is to understand how newly identified chromatin-modifying enzymes function so we can ascertain their efficacy as future therapeutic targets