The Arkansas Integrative Metabolic Research Center is set to host a seminar featuring Year Five Pilot Project Awardees, Jeff Lewis and Megan Rexius-Hall. The event will take place at 11:50 a.m. on Wednesday, September 2, in Bell Engineering 2269. Both researchers will present their findings, focusing on two innovative projects that explore critical aspects of cellular response and disease modeling.
Unveiling Protein Modifications through High-Throughput CRISPR Screens
Jeff Lewis will discuss his research on the global functional effects of post-translational protein modifications, particularly using high-throughput CRISPR screening methods. Cells must adapt quickly to environmental changes, and one of the ways they achieve this is through post-translational modifications that alter protein function. A notable modification is reversible lysine acetylation, which was traditionally thought to be limited to regulating gene transcription. However, recent findings have revealed a wider scope of acetylation across thousands of proteins in various organisms, leaving much about its functionality still to be understood.
To investigate this, Lewis’ research employs lysine substitution mutants that simulate acetylated and non-acetylated lysine residues. Despite the promise of this approach, progress has often been slow, as each lysine residue is typically tested individually. To streamline this process, Lewis’ lab has developed a high-throughput CRISPR-based method that can assess approximately 8,000 lysine sites at once under varying physiological conditions. This novel approach has led to the identification of numerous new regulatory acetylation events, significantly advancing our understanding of protein function.
Research Background: Jeff Lewis
Jeff Lewis hails from Southern California and was introduced to research during his undergraduate studies at UC-Santa Barbara. There, he explored virulence gene regulation in uropathogenic E. coli under the guidance of David Low. His journey continued at the University of Wisconsin, where he earned a Ph.D. in Microbiology, focusing on the genetics and biochemistry of unique carbon source catabolism in Salmonella enterica. Following his doctoral studies, Lewis transitioned to eukaryotic systems as a postdoctoral fellow, investigating yeast stress defense genomics. Today, his lab is dedicated to understanding how organisms sense and adapt to stressful environmental conditions and why some genetically distinct individuals exhibit greater resilience or susceptibility to stress.
Engineering In Vitro Models for Pulmonary Hypertension
Megan Rexius-Hall will present her research on engineering pulmonary hypertension (PH) in vitro, utilizing clinical pressure waveforms. Pulmonary arterial smooth muscle cells (PASMCs) are crucial in the vascular remodeling associated with PH, responding to various mechanical and biochemical signals. Traditional in vitro models often fail to replicate the dynamic conditions encountered by PASMCs in living organisms, as they typically rely on static culture environments.
To overcome these limitations, Rexius-Hall’s laboratory has created an innovative in vitro platform that allows for controlled exposure of PASMCs to dynamic pressure waveforms while simultaneously regulating oxygen levels. This platform facilitates a more accurate mimicry of the physiological conditions experienced by PASMCs in vivo. Current research efforts are focused on refining this system to ensure reproducible microenvironmental control. Future studies aim to explore how the interplay of dynamic pressure and oxygen levels affects PASMC metabolism, production of reactive oxygen species, cell proliferation, and overall cell viability. This pioneering platform lays the groundwork for investigating the complex interactions between mechanical and metabolic stressors that contribute to dysfunctional states associated with PH.
Research Background: Megan Rexius-Hall
Megan Rexius-Hall is an Assistant Professor at the Ralph E. Martin Department of Chemical Engineering, holding the Robert E. Babcock Sr. Endowed Chair. She earned her Ph.D. in Biomedical Engineering from the University of Illinois Chicago, where she received co-advising from the Departments of Biomedical Engineering and Pharmacology. Following her doctoral studies, she completed a postdoctoral fellowship at the University of Southern California in the Laboratory for Living Systems Engineering. Rexius-Hall’s contributions have garnered recognition, including an AHA Postdoctoral Fellowship and the NIH NHLBI Pathway to Independence Award (K99/R00). Leading the Microphysiological Engineering Group, she focuses on integrating cell biology, materials science, and microfabrication techniques to develop advanced microphysiological systems. Her ongoing research aims to elucidate the mechanistic foundations of various diseases and injuries, identify potential therapeutic targets, and facilitate preclinical drug screening.
Seminar Details and Participation
The seminar represents an opportunity to engage with cutting-edge research in the field of metabolic studies and engineering. Participants can look forward to a stimulating discussion that bridges theoretical knowledge and practical applications. Attendees will have the chance to enjoy pizza and beverages while networking with peers and experts in the field.
For those unable to attend in person, the seminar will also be accessible via Zoom, ensuring broad participation. This initiative is supported by the National Institutes of Health’s NIGMS under Award Number 2P20GM139768.
In summary, the upcoming AIMRC seminar will showcase pioneering research that significantly impacts our understanding of cellular mechanisms and disease states. Jeff Lewis and Megan Rexius-Hall’s innovative approaches demonstrate the potential of modern scientific techniques in addressing complex biological questions.
- Key Takeaways:
- High-throughput CRISPR screens reveal new insights into protein acetylation.
- Engineering dynamic in vitro models enhances understanding of pulmonary hypertension.
- Multidisciplinary approaches are crucial for advancing biomedical research.
This seminar promises to be an enlightening event that fosters collaboration and innovation within the life sciences community.
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