David J. J. Gresham

Associate Professor of Biology; Faculty Director of Bioinformatics


Areas of Research/Interest

Genomics of adaptive evolution, growth-rate regulation and post-transcriptional gene regulation.


Our aim is to understand the structure and behavior of the genetic networks that interpret the external environment of the cell. We use the budding yeast to study these networks using a combination of genetic, cell biology and genomic/ computational approaches. Our research addresses three fundamental questions:

  1. What are the pathways, dynamics and principles of adaptive evolution in response to environmental conditions? We perform evolution experiments over hundreds of generations in defined environments using chemostat (continuous) cultures. We study the multigenic basis of evolved quantitative phenotypes to understand the evolutionary trajectories of fitness landscapes and how genes interact to produce quantitative variation.
  2. How does post-transcriptional regulation of gene expression facilitate response to environmental conditions? The response of biological networks to dynamic environments requires processes that occur on very short timescales. The fastest means of altering transcriptional programs is through the degradation or stabilization of pre-existing transcripts. We study the mechanisms that regulate the fate of RNAs in response to environmental signals.
  3. What is the high-resolution structure of genetic interaction networks? To build a map of genetic interactions we employ high throughput suppressor screens using conditional lethal alleles. We use forward and reverse genetic approaches to explore a large fraction of sequence space allowing us to identify both those genes (and their products) that interact and the sequence specificity of those interactions. Our ultimate aim is to infer the rules that govern the interaction and co-evolution of genes.


Resolving the Complex Genetic Basis of Phenotypic Variation and Variability of Cellular Growth.
Genetics (2017 May 11) PMID: 28495957
Ziv N, Shuster BM, Siegal ML, Gresham D

Multiple Transcript Properties Related to Translation Affect mRNA Degradation Rates in Saccharomyces cerevisiae.
G3 (Bethesda) (2016 Sep 15) PMC5100846 free full-text archive
Neymotin B, Ettore V, Gresham D

Steady-state and dynamic gene expression programs in Saccharomyces cerevisiae in response to variation in environmental nitrogen.
Mol Biol Cell (2016 Apr 15) PMC4831890 free full-text archive
Airoldi EM, Miller D, Athanasiadou R, Brandt N, Abdul-Rahman F, Neymotin B, Hashimoto T, Bahmani T, Gresham D

A common mechanism involving the TORC1 pathway can lead to amphotericin B-persistence in biofilm and planktonic Saccharomyces cerevisiae populations.
Sci Rep (2016 Feb 23) PMC4763212 free full-text archive
Bojsen R, Regenberg B, Gresham D, Folkesson A

"Hit-and-Run" transcription: de novo transcription initiated by a transient bZIP1 "hit" persists after the "run".
BMC Genomics (2016 Feb 03) PMC4738784 free full-text archive
Doidy J, Li Y, Neymotin B, Edwards MB, Varala K, Gresham D, Coruzzi GM

Hst3p, a histone deacetylase, promotes maintenance of Saccharomyces cerevisiae chromosome III lacking efficient replication origins.
Mol Genet Genomics (2016 Feb) PMC4729790 free full-text archive
Irene C, Theis JF, Gresham D, Soteropoulos P, Newlon CS

Evolution: Fitness tracking for adapting populations.
Nature (2015 Mar 12) PMID: 25731163
Gresham D

The enduring utility of continuous culturing in experimental evolution.
Genomics (2014 Dec) PMC4411559 free full-text archive
Gresham D, Dunham MJ

De-novo learning of genome-scale regulatory networks in S. cerevisiae.
PLoS One (2014) PMC4162580 free full-text archive
Ma S, Kemmeren P, Gresham D, Statnikov A

Determination of in vivo RNA kinetics using RATE-seq.
RNA (2014 Oct) PMC4174445 free full-text archive
Neymotin B, Athanasiadou R, Gresham D

The functional basis of adaptive evolution in chemostats.
FEMS Microbiol Rev (2015 Jan) PMC4391987 free full-text archive
Gresham D, Hong J

Molecular specificity, convergence and constraint shape adaptive evolution in nutrient-poor environments.
PLoS Genet (2014 Jan) PMC3886903 free full-text archive
Hong J, Gresham D

Design and analysis of Bar-seq experiments.
G3 (Bethesda) (2014 Jan 10) PMC3887526 free full-text archive
Robinson DG, Chen W, Storey JD, Gresham D

The use of chemostats in microbial systems biology.
J Vis Exp (2013 Oct 14) PMC3940325 free full-text archive
Ziv N, Brandt NJ, Gresham D

Genetic and nongenetic determinants of cell growth variation assessed by high-throughput microscopy.
Mol Biol Evol (2013 Dec) PMC3840306 free full-text archive
Ziv N, Siegal ML, Gresham D

A sticky solution.
Elife (2013 Apr 02) PMC3614024 free full-text archive
Gresham D

The details in the distributions: why and how to study phenotypic variability.
Curr Opin Biotechnol (2013 Aug) PMC3732567 free full-text archive
Geiler-Samerotte KA, Bauer CR, Li S, Ziv N, Gresham D, Siegal ML

Amino acid transporter genes are essential for FLO11-dependent and FLO11-independent biofilm formation and invasive growth in Saccharomyces cerevisiae.
PLoS One (2012) PMC3406018 free full-text archive
Torbensen R, Moller HD, Gresham D, Alizadeh S, Ochmann D, Boles E, Regenberg B

High-Resolution SNP/CGH Microarrays Reveal the Accumulation of Loss of Heterozygosity in Commonly Used Candida albicans Strains.
G3 (Bethesda) (2011 Dec) PMC3276171 free full-text archive
Abbey D, Hickman M, Gresham D, Berman J

DNA microarray-based mutation discovery and genotyping.
Methods Mol Biol (2011) PMID: 22065438
Gresham D

Rational design of temperature-sensitive alleles using computational structure prediction.
PLoS One (2011) PMC3166291 free full-text archive
Poultney CS, Butterfoss GL, Gutwein MR, Drew K, Gresham D, Gunsalus KC, Shasha DE, Bonneau R

System-level analysis of genes and functions affecting survival during nutrient starvation in Saccharomyces cerevisiae.
Genetics (2011 Jan) PMC3018308 free full-text archive
Gresham D, Boer VM, Caudy A, Ziv N, Brandt NJ, Storey JD, Botstein D

Adaptation to diverse nitrogen-limited environments by deletion or extrachromosomal element formation of the GAP1 locus.
Proc Natl Acad Sci U S A (2010 Oct 26) PMC2972935 free full-text archive
Gresham D, Usaite R, Germann SM, Lisby M, Botstein D, Regenberg B

Dissection of genetically complex traits with extremely large pools of yeast segregants.
Nature (2010 Apr 15) PMC2862354 free full-text archive
Ehrenreich IM, Torabi N, Jia Y, Kent J, Martis S, Shapiro JA, Gresham D, Caudy AA, Kruglyak L

Optimized detection of sequence variation in heterozygous genomes using DNA microarrays with isothermal-melting probes.
Proc Natl Acad Sci U S A (2010 Jan 26) PMC2824413 free full-text archive
Gresham D, Curry B, Ward A, Gordon DB, Brizuela L, Kruglyak L, Botstein D

A molecular barcoded yeast ORF library enables mode-of-action analysis of bioactive compounds.
Nat Biotechnol (2009 Apr) PMC3856559 free full-text archive
Ho CH, Magtanong L, Barker SL, Gresham D, Nishimura S, Natarajan P, Koh JL, Porter J, Gray CA, Andersen RJ, Giaever G, Nislow C, Andrews B, Botstein D, Graham TR, Yoshida M, Boone C

Predicting cellular growth from gene expression signatures.
PLoS Comput Biol (2009 Jan) PMC2599889 free full-text archive
Airoldi EM, Huttenhower C, Gresham D, Lu C, Caudy AA, Dunham MJ, Broach JR, Botstein D, Troyanskaya OG

The repertoire and dynamics of evolutionary adaptations to controlled nutrient-limited environments in yeast.
PLoS Genet (2008 Dec) PMC2586090 free full-text archive
Gresham D, Desai MM, Tucker CM, Jenq HT, Pai DA, Ward A, DeSevo CG, Botstein D, Dunham MJ

Rise of the machines.
PLoS Genet (2008 Aug 01) PMC2467494 free full-text archive
Gresham D, Kruglyak L

Comparing whole genomes using DNA microarrays.
Nat Rev Genet (2008 Apr) PMID: 18347592
Gresham D, Dunham MJ, Botstein D

Coordination of growth rate, cell cycle, stress response, and metabolic activity in yeast.
Mol Biol Cell (2008 Jan) PMC2174172 free full-text archive
Brauer MJ, Huttenhower C, Airoldi EM, Rosenstein R, Matese JC, Gresham D, Boer VM, Troyanskaya OG, Botstein D

Genome-wide analysis of nucleotide-level variation in commonly used Saccharomyces cerevisiae strains.
PLoS One (2007 Mar 28) PMC1829191 free full-text archive
Schacherer J, Ruderfer DM, Gresham D, Dolinski K, Botstein D, Kruglyak L

Global mapping of transposon location.
PLoS Genet (2006 Dec 15) PMC1698948 free full-text archive
Gabriel A, Dapprich J, Kunkel M, Gresham D, Pratt SC, Dunham MJ

Accumulation of recessive lethal mutations in Saccharomyces cerevisiae mlh1 mismatch repair mutants is not associated with gross chromosomal rearrangements.
Genetics (2006 Sep) PMC1569777 free full-text archive
Heck JA, Gresham D, Botstein D, Alani E

Genome-wide detection of polymorphisms at nucleotide resolution with a single DNA microarray.
Science (2006 Mar 31) PMID: 16527929
Gresham D, Ruderfer DM, Pratt SC, Schacherer J, Dunham MJ, Botstein D, Kruglyak L

Mutation history of the roma/gypsies.
Am J Hum Genet (2004 Oct) PMC1182047 free full-text archive
Morar B, Gresham D, Angelicheva D, Tournev I, Gooding R, Guergueltcheva V, Schmidt C, Abicht A, Lochmuller H, Tordai A, Kalmar L, Nagy M, Karcagi V, Jeanpierre M, Herczegfalvi A, Beeson D, Venkataraman V, Warwick Carter K, Reeve J, de Pablo R, Kucinskas V, Kalaydjieva L

The effective mutation rate at Y chromosome short tandem repeats, with application to human population-divergence time.
Am J Hum Genet (2004 Jan) PMC1181912 free full-text archive
Zhivotovsky LA, Underhill PA, Cinnioglu C, Kayser M, Morar B, Kivisild T, Scozzari R, Cruciani F, Destro-Bisol G, Spedini G, Chambers GK, Herrera RJ, Yong KK, Gresham D, Tournev I, Feldman MW, Kalaydjieva L

Reversing Babel with GO.
Nat Genet (2002 Jul) PMID: 12089515
Gresham D

Origins and divergence of the Roma (gypsies).
Am J Hum Genet (2001 Dec) PMC1235543 free full-text archive
Gresham D, Morar B, Underhill PA, Passarino G, Lin AA, Wise C, Angelicheva D, Calafell F, Oefner PJ, Shen P, Tournev I, de Pablo R, Kucinskas V, Perez-Lezaun A, Marushiakova E, Popov V, Kalaydjieva L

Genetic studies of the Roma (Gypsies): a review.
BMC Med Genet (2001) PMC31389 free full-text archive
Kalaydjieva L, Gresham D, Calafell F

Hereditary motor and sensory neuropathy--Lom (HMSNL): refined genetic mapping in Romani (Gypsy) families from several European countries.
Neuromuscul Disord (2000 Dec) PMID: 11053686
Chandler D, Angelicheva D, Heather L, Gooding R, Gresham D, Yanakiev P, de Jonge R, Baas F, Dye D, Karagyozov L, Savov A, Blechschmidt K, Keats B, Thomas PK, King RH, Starr A, Nikolova A, Colomer J, Ishpekova B, Tournev I, Urtizberea JA, Merlini L, Butinar D, Chabrol B, Voit T, Baethmann M, Nedkova V, Corches A, Kalaydjieva L

N-myc downstream-regulated gene 1 is mutated in hereditary motor and sensory neuropathy-Lom.
Am J Hum Genet (2000 Jul) PMC1287101 free full-text archive
Kalaydjieva L, Gresham D, Gooding R, Heather L, Baas F, de Jonge R, Blechschmidt K, Angelicheva D, Chandler D, Worsley P, Rosenthal A, King RH, Thomas PK