Aidan Flynn

Program: Plant and Microbial Biosciences

Current advisor: Alex Holehouse, PhD

Undergraduate university: Washington University, 2021

Enrollment year: 2021

Research summary
 Interrogating the Intersections of Intrinsically Disordered Proteins and Evolution.

Evolution is a fundamental principle of biology that guides the inference of protein function in most approaches. However, proteins and protein regions that lack a well-defined three-dimensional structure, collectively called intrinsically disordered protein regions (IDRs), largely lack sequence conservation. Therefore, we cannot analyze them using standard evolutionary assumptions. Given how ubiquitous IDRs are across proteomes, it is of the utmost importance to gain a broader understanding of how disordered protein sequences evolve. My research uses directed evolution in yeast to identify signatures of positive selection in the evolution of transcriptional activation domains, a specific class of disordered regions that is mechanistically well understood but difficult to study through an evolutionary lens. This will provide an understanding of what parts of sequence space disordered regions sample while evolving in a cell. Ultimately, my work will provide an expansive view into the molecular evolutionary behaviors of disordered proteins.

Graduate publications
Flynn AJ, Miller K, Codjoe JM, King MR, Haswell ES. 2023 Mechanosensitive ion channels MSL8, MSL9, and MSL10 have environmentally sensitive intrinsically disordered regions with distinct biophysical characteristics in vitro. Plant Direct, 7(8):e515. PMCID: PMC10400277

Ginell GM, Flynn AJ, Holehouse AS. 2023 SHEPHARD: a modular and extensible software architecture for analyzing and annotating large protein datasets. Bioinformatics, 39(8):btad488. PMCID: PMC10423030

Prusa J, Zhu DX, Flynn AJ, Jensen D, Manzano AR, Galburt EA, Stallings CL. 2022 Molecular dissection of RbpA-mediated regulation of fidaxomicin sensitivity in mycobacteria. J Biol Chem, 298(4):101752. PMCID: PMC8956947