AIMRC Seminar: Girodat to Give Lecture on Insights From Diamond-Blackfan Anemia

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Dylan Girodat

The Arkansas Integrative Metabolic Research Center will host Dylan Girodat, assistant professor of chemistry & biochemistry at the U of A, at 12:55 p.m. on Wednesday, March 13, in Gearhart Hall 108.

Girodat will discuss how Diamond-Blackfan anemia models indicate that mutations in ribosomal proteins lead to elevated glycolysis and diminished aerobic respiration. Additionally, he will delve into the mechanistic link between protein and carbohydrate metabolism. He will address how these mutations cause instability in ribosomal proteins, creating haploinsufficient ribosomes predominantly found as subunits rather than actively translating units, thus limiting translational output.

Abstract: Ribosomopathies are diseases caused by mutations in ribosome constituents that disrupt ribosome biogenesis, impair protein synthesis and reprogram metabolic pathways. Diamond-Blackfan anemia (DBA) is a prevalent ribosomopathy resulting from mutations in the ribosomal proteins uL11, uL18 and eS19, located in the central protuberance and head domain, respectively. Hematopoietic cells of DBA patients are hypo-proliferative; however, through unknown mechanisms, they transition to hyper-proliferative states, leading to cancer. The current paradigm suggests that metabolic dysfunction in patients is the driving force behind the hyper-proliferative state. Nevertheless, the mechanistic link between protein metabolism and other metabolic pathways remains unknown. In this seminar, we will explore how DBA models indicate that mutations in ribosomal proteins lead to elevated glycolysis and diminished aerobic respiration. Additionally, we will delve into the mechanistic link between protein and carbohydrate metabolism. Moreover, we will address how these mutations cause instability in ribosomal proteins, creating haploinsufficient ribosomes predominantly found as subunits rather than actively translating units, thus limiting translational output.

Biography: Girodat has been an assistant professor in the Department of Chemistry and Biochemistry at the U of A since August 2022. He earned his Ph.D. at the University of Lethbridge in Canada, where he focused on studying the conformational dynamics of guanosine triphosphatases and the D2 dopamine receptor. Subsequently, Girodat embarked on a Director's Funded Postdoctoral Fellowship at Los Alamos National Laboratory, investigating the conformational dynamics of the ribosome during aminoacyl-tRNA selection and providing structural interpretations of long-noncoding RNA. His research at the U of A delves into understanding how perturbations to ribosomal constituents, such as mutations, are associated with diseased states, including cancer. Furthermore, his research encompasses the development of novel protein-based biosensors for the rapid and sensitive detection of carbohydrates and small metabolites. To facilitate this research, his lab employs integrative structural biology, incorporating elements of enzymes.

This event is supported by NIGMS of the National Institutes of Health under Award Number P20GM139768. The content is solely the authors' responsibility and does not necessarily represent the official views of the National Institutes of Health.

Pizza and beverages will be served. Please contact Kimberley Fuller, fullerk@uark.edu, for more information. For those unable to attend in person, this seminar will also be available via Zoom.