Alex Holehouse

Alex Holehouse
Assistant Professor

Biochemistry and Molecular Biophysics

Lab Website
Publications (PubMed / NIH)

Office: 223B McDonnell Sciences Building
Phone: 314-273-8371
Email: alex.holehouse@wustl.edu
 

Research

We explore how intrinsically disordered protein regions confer biological function and how this goes wrong in disease. The lab integrates physics-based models (all-atom and coarse-grained simulations) with informatics and machine learning to develop sequence-specific predictions. We then test those predictions either within the lab, or with collaborators around the world.

Of particular interest is understanding how disordered proteins drive self-assembly in the context of biological phase separation, with a major emphasis on understanding when, how, and why this might be important for normal cellular function.

Holehouse Research


Select Publications

Daniel Griffith & Alex S. Holehouse (2021). “PARROT is a flexible recurrent neural network framework for analysis of large protein datasets” Elife. 2021 Sep 17;10:e70576. doi: 10.7554/eLife.70576. (Abstract)

Ishan Taneja & Alex S. Holehouse (2021). “Folded domain charge properties influence the conformational behavior of disordered tails” Curr Res Struct Biol. 2021 Sep 7;3:216-228. doi: 10.1016/j.crstbi.2021.08.002. eCollection 2021. (Abstract)

Ryan J. Emenecker, Daniel Griffith, & Alex S. Holehouse (2021). “Metapredict: a fast, accurate, and easy-to-use predictor of consensus disorder and structure” Biophys J. 2021 Sep 2;S0006-3495(21)00725-6. doi: 10.1016/j.bpj.2021.08.039. Online ahead of print. (Abstract)

Yanniv Dorone, Steven Boeynaems, Eduardo Flores, Benjamin Jin, Shannon Hateley, Flavia Bossi, Elena Lazarus, Janice G. Pennington, Emiel Michiels, Mathias De Decker, Katlijn Vints, Pieter Baatsen, George W. Bassel, Marisa S. Otegui, Alex S. Holehouse, Moises Exposito-Alonso, Shahar Sukenik, Aaron D. Gitler, Seung Y. Rhee (2021). “A prion-like protein regulator of seed germination undergoes hydration-dependent phase separation” Cell. 2021 Aug 5;184(16):4284-4298.e27. doi: 10.1016/j.cell.2021.06.009. Epub 2021 Jul 6. (Abstract)

Shubhanjali Minhas & Alex S. Holehouse (2021). “Step on the cGAS! Viral inhibition of cGAS phase separation with cytosolic DNA” Mol Cell. 2021 Jul 1;81(13):2688-2689. doi: 10.1016/j.molcel.2021.06.007. (Abstract)

Ryan J. Emenecker, Alex S. Holehouse, & Lucia C. Strader (2021). “Sequence determinants of in cell condensate morphology, dynamics, and oligomerization as measured by number and brightness analysis” Cell Commun Signal. 2021 Jun 5;19(1):65. doi: 10.1186/s12964-021-00744-9. (Abstract)

E. Sethe Burgie, Zachary T. K. Gannam, Katrice E. McLoughlin, Christopher D. Sherman, Alex S. Holehouse, Robert J. Stankey, & Richard D. Vierstra (2021). “Differing biophysical properties underpin the unique signaling potentials within the plant phytochrome photoreceptor families” Proc Natl Acad Sci U S A. 2021 Jun 1;118(22):e2105649118. doi: 10.1073/pnas.2105649118. (Abstract)

Jasmine Cubuk, Jhullian J. Alston, J. Jeremías Incicco, Sukrit Singh, Melissa D. Stuchell-Brereton, Michael D. Ward, Maxwell I. Zimmerman, Neha Vithani, Daniel Griffith, Jason A. Wagoner, Gregory R. Bowman, Kathleen B. Hall, Andrea Soranno, & Alex S. Holehouse. (2021). “The SARS-CoV-2 nucleocapsid protein is dynamic, disordered, and phase separates with RNA” Nat Commun. 2021 Mar 29;12(1):1936. doi: 10.1038/s41467-021-21953-3. (Abstract)

Jason D Fernandes, Sarvenaz Sarabipour, Christopher T Smith, Natalie M Niemi, Nafisa M Jadavji, Ariangela J Kozik, Alex S Holehouse, Vikas Pejaver, Orsolya Symmons, Alexandre W Bisson Filho, & Amanda Haage (2020). “A survey-based analysis of the academic job market” Elife. 2020 Jun 12;9:e54097. doi: 10.7554/eLife.54097. Online ahead of print. (Abstract)

Holehouse A.S. & Sukenik S. (2020). “Controlling Structural Bias in Intrinsically Disordered Proteins Using Solution Space Scanning.” J Chem Theory Comput. 2020 Mar 10;16(3):1794-1805. doi: 10.1021/acs.jctc.9b00604. Epub 2020 Feb 17. (Abstract)

Rawlings A.E., Liravi P., Corbett S., Holehouse A.S., & Staniland S.S. (2020). “Investigating the ferric ion binding site of magnetite biomineralisation protein Mms6.” PLoS One. 2020 Feb 25;15(2):e0228708. doi: 10.1371/journal.pone.0228708. eCollection 2020. (Abstract)

Martin E.W., Holehouse A.S., Peran I., Farag M., Incicco J.J., Bremer A., Grace C.R., Soranno A., Pappu R.V., & Mittag T. (2020). “Valence and patterning of aromatic residues determine the phase behavior of prion-like domains.” Science. 2020 Feb 7;367(6478):694-699. doi: 10.1126/science.aaw8653. (Abstract)

Greig J.A., Nguyen T.A., Lee M., Holehouse A.S., Posey A.E., Pappu R.V., & Jedd G. (2020). “Arginine-Enriched Mixed-Charge Domains Provide Cohesion for Nuclear Speckle Condensation.” Mol Cell. 2020 Feb 6. pii: S1097-2765(20)30046-0. doi: 10.1016/j.molcel.2020.01.025. [Epub ahead of print] (Abstract)

Choi J.M., Holehouse A.S., & Pappu R.V. (2020). “Physical Principles Underlying the Complex Biology of Intracellular Phase Transitions.” Annu Rev Biophys. 2020 Jan 31. doi: 10.1146/annurev-biophys-121219-081629. [Epub ahead of print] (Abstract)

Harding R.J., Loppnau P., Ackloo S., Lemak A., Hutchinson A., Hunt B., Holehouse A.S., Ho J.C., Fan L., Toledo-Sherman L., Seitova A., & Arrowsmith C.H. (2019). “Design and characterization of mutant and wildtype huntingtin proteins produced from a toolkit of scalable eukaryotic expression systems.” J Biol Chem. 2019 Apr 26;294(17):6986-7001. doi: 10.1074/jbc.RA118.007204. Epub 2019 Mar 6. (Abstract)