Biologist leads new $1.8 million gene regulation study
A biologist at The University of Texas at Arlington is leading a $1.8 million federally funded project to study the molecular processes affecting gene regulation to better understand how small genetic pathways called RNAi (ribonucleic acid interference) impact human health. The hope is that this improved genetic knowledge will aid the development of synthetic therapies to treat or prevent diseases like cancer.
“Defects in RNAi cause devastating gene dysregulation, allowing some genes to wreak havoc on the genome, resulting in the onset of cancers, infertility, neurodegenerative disorders and many other diseases,” said Assistant Professor of biology Alicia Rogers, lead investigator on the project. “It is critical we learn how balancing between the interdependent RNAi pathways is maintained and how RNAi homeostasis is impacted by real-world stresses to advance our understanding of RNAi in human health and disease.”
Found in all living cells, RNA is involved in protein synthesis, which is the process of turning genetic instructions into proteins in cells. While some types of RNA provide the template for protein sequences, other non-coding types are involved in regulating gene expression, which in turn affects many biological processes.
RNAi is a cellular mechanism that uses small RNA complementary to the gene’s DNA sequence to regulate the gene, a process that scientists call silencing.
Dr. Rogers’ grant from the National Institute of General Medicine Sciences (part of the National Institutes of Health) builds upon data from her recently published study in Nucleic Acids Research on small RNA pathway function. Trilotma Sen, a doctoral student in Rogers’ lab, and Cara McCormick, a former research technician in her lab, were co-authors on that paper.
The focus of the project is to study how small RNA pathways regulate genes and protect them from stressors. Rogers, Sen, and doctoral student Ha Meem hope to gain a fundamental understanding of this process, with the long-term goal of harnessing that knowledge to find ways to prevent and treat diseases in humans.
They will carry out their research using the microscopic worm C. elegans as their model system because it’s where small RNA pathways were first discovered.
“It’s a beautiful model system where we have a lot of genetic control,” Rogers said. “The animal is transparent so we can image and use microscopy to study these pathways in conjunction with molecular biology and genetics. Even though it’s a microscopic worm, because these pathways are evolutionarily conserved, the principles that we’re going to hopefully uncover will be applicable to the way that the pathways work in humans.”
The team has three main areas of emphasis in the study: the mechanisms of target transcript sorting among distinct RNAi branches; how RNAi pathways are temporally regulated throughout development; and the molecular and physiological consequences of disrupting RNAi homeostasis.
“Addressing these fundamental questions is critical for our understanding of small RNAs in human health. This knowledge is important for the development of bioengineering techniques that harness the power of our own regulatory networks for use in therapeutic synthetic gene regulation,” Rogers said.