David J. J. Gresham

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.

Date of these PubMed search results: March 24 2020
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1. Gene regulatory network reconstruction using single-cell RNA sequencing of barcoded genotypes in diverse environments.
   Elife (2020 Jan 27) PMC7004572 free full-text archive
   Jackson CA, Castro DM, Saldi GA, Bonneau R, Gresham D
2. An evolving view of copy number variants.
   Curr Genet (2019 Dec) PMID: 31076843
   Lauer S, Gresham D
3. A complete statistical model for calibration of RNA-seq counts using external spike-ins and maximum likelihood theory.
   PLoS Comput Biol (2019 Mar) PMC6428340 free full-text archive
   Athanasiadou R, Neymotin B, Brandt N, Wang W, Christiaen L, Gresham D, Tranchina D
4. Single-cell copy number variant detection reveals the dynamics and diversity of adaptation.
   PLoS Biol (2018 Dec) PMC6298651 free full-text archive
   Lauer S, Avecilla G, Spealman P, Sethia G, Brandt N, Levy SF, Gresham D
5. Evaluating the Feasibility and Effectiveness of an Australian Safety Planning Smartphone Application: A Pilot Study Within a Tertiary Mental Health Service.
   Suicide Life Threat Behav (2019 Jun) PMC6618059 free full-text archive
   Melvin GA, Gresham D, Beaton S, Coles J, Tonge BJ, Gordon MS, Stanley B
6. Systematic identification of factors mediating accelerated mRNA degradation in response to changes in environmental nitrogen.
   PLoS Genet (2018 May) PMC5983874 free full-text archive
   Miller D, Brandt N, Gresham D
7. An incoherent feedforward loop facilitates adaptive tuning of gene expression.
   Elife (2018 Apr 5) PMC5903863 free full-text archive
   Hong J, Brandt N, Abdul‑Rahman F, Yang A, Hughes T, Gresham D
8. Determining mRNA Decay Rates Using RNA Approach to Equilibrium Sequencing (RATE-Seq).
   Methods Mol Biol (2018) PMID: 29236248
   Abdul‑Rahman F, Gresham D
9. Incorporation of unique molecular identifiers in TruSeq adapters improves the accuracy of quantitative sequencing.
   Biotechniques (2017 Nov 1) PMID: 29185922
   Hong J, Gresham D
10. Resolving the Complex Genetic Basis of Phenotypic Variation and Variability of Cellular Growth.
    Genetics (2017 Jul) PMC5500157 free full-text archive
    Ziv N, Shuster BM, Siegal ML, Gresham D
11. Multiple Transcript Properties Related to Translation Affect mRNA Degradation Rates in Saccharomyces cerevisiae.
    G3 (Bethesda) (2016 Nov 8) PMC5100846 free full-text archive
    Neymotin B, Ettorre V, Gresham D
12. 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
13. 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
14. "Hit-and-Run" transcription: de novo transcription initiated by a transient bZIP1 "hit" persists after the "run".
    BMC Genomics (2016 Feb 3) PMC4738784 free full-text archive
    Doidy J, Li Y, Neymotin B, Edwards MB, Varala K, Gresham D, Coruzzi GM
15. 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
16. Evolution: Fitness tracking for adapting populations.
    Nature (2015 Mar 12) PMID: 25731163
    Gresham D
17. The enduring utility of continuous culturing in experimental evolution.
    Genomics (2014 Dec) PMC4411559 free full-text archive
    Gresham D, Dunham MJ
18. 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
19. Determination of in vivo RNA kinetics using RATE-seq.
    RNA (2014 Oct) PMC4174445 free full-text archive
    Neymotin B, Athanasiadou R, Gresham D
20. The functional basis of adaptive evolution in chemostats.
    FEMS Microbiol Rev (2015 Jan) PMC4391987 free full-text archive
    Gresham D, Hong J
21. 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
22. 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
23. 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
24. 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
25. A sticky solution.
    Elife (2013 Apr 2) PMC3614024 free full-text archive
    Gresham D
26. 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
27. 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
28. 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
29. DNA microarray-based mutation discovery and genotyping.
    Methods Mol Biol (2011) PMID: 22065438
    Gresham D
30. 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
31. 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
32. 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
33. 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
34. 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
35. 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 JLY, Porter J, Gray CA, Andersen RJ, Giaever G, Nislow C, Andrews B, Botstein D, Graham TR, Yoshida M, Boone C
36. 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
37. 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
38. Rise of the machines.
    PLoS Genet (2008 Aug 1) PMC2467494 free full-text archive
    Gresham D, Kruglyak L
39. Comparing whole genomes using DNA microarrays.
    Nat Rev Genet (2008 Apr) PMID: 18347592
    Gresham D, Dunham MJ, Botstein D
40. 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
41. 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
42. 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
43. 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
44. 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
45. 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
46. 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
47. Reversing Babel with GO.
    Nat Genet (2002 Jul) PMID: 12089515
    Gresham D
48. 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
49. Genetic studies of the Roma (Gypsies): a review.
    BMC Med Genet (2001) PMC31389 free full-text archive
    Kalaydjieva L, Gresham D, Calafell F
50. 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
51. 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