Investigator:
Brianne Rogers, PhD
Name of Institution:
HudsonAlpha Institute for Biotechnology
Project Title:
Mechanisms of SNCA regulation
Investigator Bio:
Dr. Rogers is a post-doctoral fellow at the HudsonAlpha Institute for Biotechnology. She received her PhD in Genetics from the University of Alabama at Birmingham in 2023. During her doctoral studies, she worked in the laboratory of Dr. Richard Myers at the HudsonAlpha Institute for Biotechnology. Dr. Rogers is currently working under the guidance of Dr. Nick Cochran with a primary focus on neurodegenerative diseases, particularly Parkinson’s disease (PD), Alzheimer’s disease (AD), and related dementias. Her research efforts are focused on understanding the role of gene regulatory elements and variation within these elements in the development of dementia. She employs high-throughput genomics technologies to identify novel gene regulatory elements for neurodegenerative disease-associated genes, aiming to identify new therapeutic targets.
Objective:
To comprehensively understand the regulatory elements controlling expression of SNCA, the gene that encodes alpha-synuclein (a-syn), and their genetic variation in populations, with the goal of identifying new therapeutic targets for PD.
Background:
Only about 1% of the human genome encodes proteins which play important roles in cells throughout the body. The remaining DNA sequences are noncoding and believed to be regulatory elements that help ensure that genes are turned on or turned off at the right time, in the right cell types, and in the right amount. The most abundant regulatory elements are enhancers, which increase the rate at which specific genes are turned on. Targeting these enhancers to reduce a gene’s expression is a new therapeutic avenue that may be beneficial in cases where an increase in a gene’s expression causes disease. However, we need a comprehensive understanding of gene regulation to identify these potential drug targets. Here, I propose to study the regulatory elements controlling expression of the SNCA gene, which encodes a-syn that is pathologically found in Lewy bodies in people with PD.
Methods/Design:
In this project, I will first determine if sequences predicted to regulate SNCA are enhancers or not by testing whether they increase transcriptional activity using advanced techniques designed to measure genetic changes at the cellular level. I will also test genetic variation observed in PD patients to determine if these variants disrupt regulatory function. Because enhancers can often act on more than one gene and in regions of the genome that are distant from the target, I will validate that these regulatory elements are controlling SNCA by using a highly specific technique called CRISPR interference. By manipulating these regions and then measuring gene expression, I can validate that the selected region is controlling SNCA expression.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Having a comprehensive understanding of SNCA regulatory elements and their genetic variation that affects SNCA expression can help expand potential therapeutic avenues for PD treatment.