Ilyas Yildirim, Ph.D., an Assistant Professor in the
Department of Chemistry and Biochemistry, was awarded $419,485 through the National Institutes of Health (NIH) for a program focused on making exploitable predictions on challenging DNA and RNA systems. Yildirim, principal investigator based out of FAU’s Jupiter campus, received the grant for the project titled, “In Silico Drug Design Targeting RNA Repeat Expansions.” The team is developing computational methods and models, which gives them unique capabilities to study biological systems and are actively collaborating with experimental researchers.
Yildirim is working with Matthew Disney, Ph.D., from the UF Scripps Research Institute. The team is developing computational methods and models, which gives them unique capabilities to study biological systems and are actively collaborating with experimental researchers.
Globally, the research program will help to find solutions to cure neuromuscular diseases such as Huntington's Disease, Myotonic Dystrophy and Fragile X-syndrome, for which there are presently no known cures or effective treatments. Furthermore, success of the proposed research program will open new doors to study protein-RNA interactions, and other types of important diseases such as HIV, Influenza and coronaviruses.
RNA orchestrates how critical biological functions are controlled, including catalysis, gene expression, enzymatic activities, and protein folding. Misregulation of gene expression cause dysregulation of RNA, which cause many heritable diseases such as Myotonic Dystrophy, Huntington’s disease, and Fragile X Syndrome caused by RNA transcripts that contain expanded repeats. The proposal seeks to create unique computational tools to investigate interaction of small molecules and ligands with dynamic RNA loops and design novel compounds by optimizing lead compounds targeting RNA repeat expansions via inclusion of functional groups. Results will be used to facilitate drug design targeting RNA.
We are a theoretical and computational chemistry group specializing in nucleic acid chemistry. Our overall goal is to make exploitable predictions on challenging DNA and RNA systems while collaborating with researchers working on biomedicine and biochemistry. We are developing computational methods and models, which give us unique capabilities to study biological systems. For this purpose, we are actively collaborating with experimental researchers to test our hypotheses and develop theoretical interpretations. Our research is motivated by understanding the physico-chemical properties of nucleic acid systems using computational methods that will provide atomistic details and directions in the development of cures to human diseases.
Over the past decade, RNA based therapeutics have become a hot research topic in the field. For example, companies such as Isis, Alnylam, Sarepta, and MODERNA are trying to develop RNA based therapeutics using antisense technology and have plans to commercialize micro-RNA based therapeutics soon. Therefore, the results of the proposed research program, which will discover the molecular mechanisms behind RNA repeat expansions, will have positive consequences in RNA-based therapeutics. The atomistic details of the dynamic RNA internal loops we will discover will yield design principles for in silico drug discovery targeting RNA molecules. Globally, the research program will help finding solutions to cure neuromuscular diseases such as Huntington's Disease, Myotonic Dystrophy, and Fragile X-syndrome, for which there are presently no known cures or effective treatments. Furthermore, success of the proposed research program will open new doors to study protein-RNA interactions, and other types of important diseases such as HIV, Influenza, and coronaviruses as well as yielding design rules for antagomirs targeting microRNA based metabolic diseases.
Our lab has extensive theoretical and computational experience with RNA molecules and RNA repeat expansions. We envision this work will expedite the process for developing targeted therapies for genetic diseases. This research, which combines exciting yet complementary disciplines of chemistry, physics, neuroscience, and computer science, will provide a strong training experience for the diverse students in my lab, and equip them with the tools to pursue advanced research that can transform the field of drug development for RNA molecules.
The long-term goal of this project is to develop a fast and accurate computational tool that facilitates drug design specifically targeting dynamic RNA structures. Achievement of this goal will assist experimentalists in rational design of small molecules targeting RNA-related human diseases.