D. Allan Drummond, Ph.D.

Assistant Professor

Research Description

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.

Selected Publications

Reversible, Specific, Active Aggregates of Endogenous Proteins Assemble upon Heat Stress.
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
(2015 Sep) Cell. 2015 Sep 10;162(6):1286-98. doi: 10.1016/j.cell.2015.08.041. 26359986 (Full Text)

Dying mRNA Tells a Story of Its Life.
Wallace EW, Drummond DA
(2015 Jun) Cell. 2015 Jun 4;161(6):1246-8. doi: 10.1016/j.cell.2015.05.043. 26046434

Accounting for experimental noise reveals that mRNA levels, amplified by post-transcriptional processes, largely determine steady-state protein levels in yeast.
Csardi G, Franks A, Choi DS, Airoldi EM, Drummond DA
(2015 May) PLoS Genet. 2015 May 7;11(5):e1005206. doi: 10.1371/journal.pgen.1005206. eCollection 2015 May. 25950722 (Full Text)

Estimating selection on synonymous codon usage from noisy experimental data.
Wallace EW, Airoldi EM, Drummond DA
(2013 Jun) Mol Biol Evol. 2013 Jun;30(6):1438-53. doi: 10.1093/molbev/mst051. Epub 2013 Mar 14. 23493257 (Full Text)

Quantifying condition-dependent intracellular protein levels enables high-precision fitness estimates.
Geiler-Samerotte KA, Hashimoto T, Dion MF, Budnik BA, Airoldi EM, Drummond DA
(2013) PLoS One. 2013 Sep 25;8(9):e75320. doi: 10.1371/journal.pone.0075320. eCollection 2013. 24086506 (Full Text)

Good codons, bad transcript: large reductions in gene expression and fitness arising from synonymous mutations in a key enzyme.
Agashe D, Martinez-Gomez NC, Drummond DA, Marx CJ
(2013 Mar) Mol Biol Evol. 2013 Mar;30(3):549-60. doi: 10.1093/molbev/mss273. Epub 2012 Dec 4. 23223712 (Full Text)

How infidelity creates a sticky situation.
Drummond DA
(2012 Dec) Mol Cell. 2012 Dec 14;48(5):663-4. doi: 10.1016/j.molcel.2012.11.024. 23244760 (Full Text)

Misfolded proteins impose a dosage-dependent fitness cost and trigger a cytosolic unfolded protein response in yeast.
Geiler-Samerotte KA, Dion MF, Budnik BA, Wang SM, Hartl DL, Drummond DA
(2011 Jan) Proc Natl Acad Sci U S A. 2011 Jan 11;108(2):680-5. doi: 10.1073/pnas.1017570108. Epub 2010 Dec 27. 21187411 (Full Text)

Mistranslation-induced protein misfolding as a dominant constraint on coding-sequence evolution.
Drummond DA, Wilke CO
(2008 Jul) Cell. 2008 Jul 25;134(2):341-52. doi: 10.1016/j.cell.2008.05.042. 18662548 (Full Text)

Why highly expressed proteins evolve slowly.
Drummond DA, Bloom JD, Adami C, Wilke CO, Arnold FH
(2005 Oct) Proc Natl Acad Sci U S A. 2005 Oct 4;102(40):14338-43. Epub 2005 Sep 21. 16176987 (Full Text)