Summary table
Research focus key words |
Transcription Regulation of gene expression SUMO post-translational modifications (Sumoylation) |
Methodologies used |
Budding yeast as a model organism Molecular biology Genomics technologies (e.g. ChIP-seq) Biochemistry Yeast genetics |
Description of research interests of our lab
Research in the lab aims to understand how cells control expression of genes during normal growth and in response to environmental stress. There are two main research areas in the lab, as described below.
If you are interested in joining the lab to carry our research, visit our Research Opportunities page.
1. Regulation of gene expression by SUMO post-translational modifications
Post-translational modifications (PTMs) play important, often essential, roles in practically every cellular process. Sumoylation is a PTM that involves attachment of the SUMO peptide to specific lysine side chains on target proteins. Sumoylation is an essential and widespread modification that targets hundreds of proteins involved in many cellular processes in all eukaryotes. The effects of protein modification by SUMO vary depending on the target protein, but include changes to localization, stability, and activity of the target.
The lab is interested in sumoylation because numerous proteins involved in gene expression are known targets of SUMO modification. In particular, many transcription factors are sumoylated, but in most cases, it is not known why they are modified, nor how sumoylation affects their function. Research in the lab aims to characterize how transcription is regulated by sumoylation of individual proteins and how genome-wide transcription can be coordinately controlled by sumoylation.
Interestingly, the number of proteins that are sumoylated in cells increases dramatically during exposure to stress, like heat shock. Furthermore, many sumoylation enzymes are over-expressed in tumours, presumably resulting in high levels of sumoylated proteins in cancer cells. Therefore, another goal of the lab is to determine how changes to cellular sumoylation levels affect gene expression genome-wide. For example, can increased sumoylation during heat shock allow the cell to focus on expression of heat shock genes?
2. Activation and reinitiation of transcription by RNA Polymerase II
In eukaryotic cells, RNA Polymerase II (RNAP II) is responsible for transcribing all protein-coding genes as well as a number of non-coding RNA genes. When a cell requires production of a specific protein or gene product, its gene is “turned on” by the process of transcriptional activation. This involves a step-wise assembly of a number of transcription factors and related complexes on the gene’s promoter, which enables the recruitment of RNAP II. RNAP II then initiates transcription of the gene.
The details of transcriptional activation have been studied for decades and are quite well-understood at many levels. However, not much is known about what happens to the promoter-bound transcription factors after the first molecule of RNAP II has initiated transcription. Research in the lab addresses this by studying how transcriptional activators, general transcription factors, and other promoter-bound complexes are regulated to make sure that further rounds of transcription can take place (i.e. reinitiation of transcription), and to ensure that the cell can shut down transcription of genes when their gene products are no longer needed.
Approaches and Techniques Used in the Lab
Budding yeast, a popular model organism, is primarily used as a biological system with a combination of molecular biology, genomics technologies (e.g. ChIP-seq), biochemistry and yeast genetics approaches. Examples of commonly used procedures include chromatin immunoprecipitation (ChIP), western blotting, protein immunoprecipitation, and quantitative RT-PCR.
Publications
See a list of Rosonina publications
Current Funding
NSERC Discovery Grant
CIHR Operating Grant