The Faculty

Focus

Function and molecular basis of rapid, reversible assembly of proteins and RNA into massive heterogeneous structures in response to cellular stress

Education

Ph.D., Computation & Neural Systems, California Institute of Technology

B.S.E., Mechanical & Aerospace Engineering, Princeton UniversityResearch Summary / Selected Publications

Research Interests

What are the spectrum, frequency and consequences of errors in protein synthesis? How do eukaryotic cells sense and respond to misfolded proteins, particularly in the cytosol? How does stochasticity in protein synthesis alter the composition and stability of the proteome? Are some errors beneficial? Does error-induced protein misfolding influence the progression of neurodegenerative diseases such as ALS?

We are pursuing mechanistic answers to these questions, taking a biochemical and genetic approach, with an emphasis on developing high-resolution, high-mass-accuracy mass spectrometric techniques for proteome-scale quantitation. From a theoretical standpoint, we are interested in understanding the imprints that natural selection on fidelity and misfolding leave on evolving genes and genomes.

Select Papers

Wallace EW, Kear-Scott JL, Pilipenko EV, Schwartz MH, Laskowski PR, Rojek AE, Katanski CD, Riback JA, Dion MF, Franks AM, Airoldi EM, Pan T, Budnik BA, Drummond DA.“Reversible, Specific, Active Aggregates of Endogenous Proteins Assemble upon Heat Stress.”Cell. Sep 10;162(6):1286-98. doi: 10.1016/j.cell.2015.08.041 (2015).

Geiler-Samerotte, K.A., Dion, M.F., Budnik, B.A., Hartl, D.L., and Drummond, D.A., “Misfolded proteins impose a dosage-dependent fitness cost and trigger a cytosolic unfolded protein response in yeast,” Proc. Nat’l. Acad. Sci. USA 180(2):680–685 (2011). 

Drummond, D.A. and Wilke, C.O., “Mistranslation-induced protein misfolding as a dominant constraint on coding-sequence evolution,” Cell 134(2):341–52 (2008).  

Drummond, D.A., Bloom, J.D., Adami, C., Wilke, C.O., and Arnold, F.H., “Why highly expressed proteins evolve slowly,” Proc. Nat’l. Acad. Sci. USA 102(40):14338–43 (2005). 

Drummond, D.A., Bloom, J.D., Adami, C., Wilke, C.O., and Arnold, F.H., “Why highly expressed proteins evolve slowly,” Proc. Nat'l. Acad. Sci. USA 102(40):14338–14343 (2005).

Drummond, D.A., Raval, A., and Wilke, C.O., “A single determinant dominates the rate of yeast protein evolution,” Molecular Biology and Evolution 23(2):327–337 (2006).

Wilke, C.O. and Drummond, D.A., “Population genetics of translational robustness,” Genetics 173:473–481 (2006).

Drummond, D.A. and Wilke, C.O., “Mistranslation-induced protein misfolding as a dominant constraint on coding-sequence evolution,” Cell 134(2):341–52 (2008).

Drummond, D.A., Silberg, J.J., Meyer, M.M., Wilke, C.O., and Arnold, F.H., “On the conservative nature of intragenic recombination,” Proc. Nat’l. Acad. Sci. USA 102(15):5380–5385 (2005).

Drummond, D.A., Iverson, B.L., Georgiou, G.G., and Arnold, F.H., “Why high-error-rate mutagenesis libraries are enriched in functional and improved proteins,” Journal of Molecular Biology 350(4):806–816 (2005).