About

Gerald R. Fink is the Margaret and Herman Sokol Professor Emeritus, American Cancer Society Professor of Genetics, and a Core Member at the Whitehead Institute. His research investigates how fungal pathogens invade the body, evade the immune system, and establish infections. Using genetics, biochemistry, and genomics, his work addresses questions such as what makes Candida albicans a successful pathogen, how fungal pathogens evolve antibiotic resistance, and how they change their genetic composition rapidly. The Fink lab focuses on molecules that enable fungi to penetrate tissues and grow in hostile environments. His notable contributions include studies on yeast genetics, molecular biology, and the mechanisms of fungal pathogenicity.

Research topics

• Biology
• Genetics
• Cell biology
• Biochemistry
• Chemistry

Selected publications

• Engineered yeast tolerance enables efficient production from toxified lignocellulosic feedstocks

  Science Advances · 2021-06-25 · 49 citations

  articleOpen accessCorresponding

  that engineered aldehyde reduction and elevated extracellular potassium and pH are sufficient to enable near-parity production between inhibitor-laden and inhibitor-free feedstocks. By specifically targeting the universal hydrolysate inhibitors, a single strain is enhanced to tolerate a broad diversity of highly toxified genuine feedstocks and consistently achieve industrial-scale titers (cellulosic ethanol of >100 grams per liter when toxified). Furthermore, a functionally orthogonal, lightweight design enables seamless transferability to existing metabolically engineered chassis strains: We endow full, multifeedstock tolerance on a xylose-consuming strain and one producing the biodegradable plastics precursor lactic acid. The demonstration of "drop-in" hydrolysate competence enables the potential of cost-effective, at-scale biomass utilization for cellulosic fuel and nonfuel products alike.

  PublisherOA PDFDOI

• A Morgan Legacy

  Genetics · 2020-11-01

  articleOpen access1st authorCorresponding

  The Thomas Hunt Morgan Medal recognizes lifetime contributions to the field of genetics. The 2020 recipient is Gerald R. Fink of Massachusetts Institute of Technology and the Whitehead Institute for Biomedical Research, recognizing the discovery of principles central to genome organization and regulation in eukaryotic cells.

  PublisherOA PDFDOI

• Xrn1p acts at multiple steps in the budding-yeast RNAi pathway to enhance the efficiency of silencing

  Nucleic Acids Research · 2020-05-21 · 4 citations

  articleOpen access

  Abstract RNA interference (RNAi) is a gene-silencing pathway that can play roles in viral defense, transposon silencing, heterochromatin formation and post-transcriptional gene silencing. Although absent from Saccharomyces cerevisiae, RNAi is present in other budding-yeast species, including Naumovozyma castellii, which have an unusual Dicer and a conventional Argonaute that are both required for gene silencing. To identify other factors that act in the budding-yeast pathway, we performed an unbiased genetic selection. This selection identified Xrn1p, the cytoplasmic 5′-to-3′ exoribonuclease, as a cofactor of RNAi in budding yeast. Deletion of XRN1 impaired gene silencing in N. castellii, and this impaired silencing was attributable to multiple functions of Xrn1p, including affecting the composition of siRNA species in the cell, influencing the efficiency of siRNA loading into Argonaute, degradation of cleaved passenger strand and degradation of sliced target RNA.

  PublisherOA PDFDOI

• Complex modifier landscape underlying genetic background effects

  Proceedings of the National Academy of Sciences · 2019-02-25 · 53 citations

  articleOpen access

  The phenotypic consequence of a given mutation can be influenced by the genetic background. For example, conditional gene essentiality occurs when the loss of function of a gene causes lethality in one genetic background but not another. Between two individual Saccharomyces cerevisiae strains, S288c and Σ1278b, ∼1% of yeast genes were previously identified as “conditional essential.” Here, in addition to confirming that some conditional essential genes are modified by a nonchromosomal element, we show that most cases involve a complex set of genomic modifiers. From tetrad analysis of S288C/Σ1278b hybrid strains and whole-genome sequencing of viable hybrid spore progeny, we identified complex sets of multiple genomic regions underlying conditional essentiality. For a smaller subset of genes, including CYS3 and CYS4 , each of which encodes components of the cysteine biosynthesis pathway, we observed a segregation pattern consistent with a single modifier associated with conditional essentiality. In natural yeast isolates, we found that the CYS3 / CYS4 conditional essentiality can be caused by variation in two independent modifiers, MET1 and OPT1 , each with roles associated with cellular cysteine physiology. Interestingly, the OPT1 allelic variation appears to have arisen independently from separate lineages, with rare allele frequencies below 0.5%. Thus, while conditional gene essentiality is usually driven by genetic interactions associated with complex modifier architectures, our analysis also highlights the role of functionally related, genetically independent, and rare variants.

  PublisherOA PDFDOI

• Xrn1p Acts at Multiple Steps in the Budding-Yeast RNAi Pathway to Enhance the Efficiency of Silencing

  bioRxiv (Cold Spring Harbor Laboratory) · 2019-12-12 · 2 citations

  preprintOpen access

  Abstract RNA interference (RNAi) is a gene-silencing pathway that can play roles in viral defense, transposon silencing, heterochromatin formation, and post-transcriptional gene silencing. Although absent from Saccharomyces cerevisiae , RNAi is present in other budding-yeast species, including Naumovozyma castellii , which have an unusual Dicer and a conventional Argonaute that are both required for gene silencing. To identify other factors that act in the budding-yeast pathway, we performed an unbiased genetic selection. This selection identified Xrn1p, the cytoplasmic 5′-to-3′ exoribonuclease, as a cofactor of RNAi in budding yeast. Deletion of XRN1 impaired gene silencing in N. castellii , and this impaired silencing was attributable to multiple functions of Xrn1p, including affecting the composition of siRNA species in the cell, influencing the efficiency of siRNA loading into Argonaute, degradation of cleaved passenger strand, and degradation of sliced target RNA.

  PublisherOA PDFDOI

• Excised linear introns regulate growth in yeast

  Nature · 2019-01-16 · 172 citations

  articleOpen access
  PublisherOA PDFDOI

• m6A modification of a 3′ UTR site reduces RME1 mRNA levels to promote meiosis

  Nature Communications · 2019-07-30 · 82 citations

  articleOpen accessSenior author

  Abstract Despite the vast number of modification sites mapped within mRNAs, known examples of consequential mRNA modifications remain rare. Here, we provide multiple lines of evidence to show that Ime4p, an N 6-methyladenosine (m 6 A) methyltransferase required for meiosis in yeast, acts by methylating a site in the 3′ UTR of the mRNA encoding Rme1p, a transcriptional repressor of meiosis. Consistent with this mechanism, genetic analyses reveal that IME4 functions upstream of RME1 . Transcriptome-wide, RME1 is the primary message that displays both increased methylation and reduced expression in an Ime4p-dependent manner. In yeast strains for which IME4 is dispensable for meiosis, a natural polymorphism in the RME1 promoter reduces RME1 transcription, obviating the requirement for methylation. Mutation of a single m 6 A site in the RME1 3′ UTR increases Rme1p repressor production and reduces meiotic efficiency. These results reveal the molecular and physiological consequences of a modification in the 3′ UTR of an mRNA.

  PublisherOA PDFDOI

• Critical Roles of the Pentose Phosphate Pathway and GLN3 in Isobutanol-Specific Tolerance in Yeast

  Cell Systems · 2019-11-13 · 43 citations

  articleOpen access
  PublisherOA PDFDOI

• Excised linear introns regulate growth in yeast

  bioRxiv (Cold Spring Harbor Laboratory) · 2018-09-25 · 2 citations

  preprintOpen access

  Abstract Spliceosomal introns are ubiquitous non-coding RNAs typically destined for rapid debranching and degradation. Here, we describe 34 excised Saccharomyces cerevisiae introns that, although rapidly degraded in log-phase growth, accumulate as linear RNAs under either saturated-growth conditions or other stresses that cause prolonged inhibition of TORC1, a key integrator of growth signaling. Introns that become stabilized remain associated with components of the spliceosome and differ from the other spliceosomal introns in having a short distance between their lariat branch point and 3′ splice site, which is necessary and sufficient for their stabilization. Deletion of these unusual introns is disadvantageous in saturated conditions and causes aberrantly high growth rates of yeast chronically challenged with the TORC1 inhibitor rapamycin. Reintroduction of native or engineered stable introns suppresses this aberrant rapamycin response. Thus, excised introns function within the TOR growth-signaling network of S. cerevisiae , and more generally, excised spliceosomal introns can have biological functions.

  PublisherOA PDFDOI

• Galectin-3 Regulates γ-Herpesvirus Specific CD8 T Cell Immunity

  iScience · 2018-10-16 · 31 citations

  articleOpen access

  T cells may therefore serve to enhance response to efficiently control infections.

  PublisherOA PDFDOI

Recent grants

• Genetic Control of Nutrition Starvation in Yeast

  NIH · $11.8M · 1984–2018

• NIH Grant R01GM040266

  NIH · $13.0M · 2014

• NIH Grant R37GM035010

  NIH · $3.7M · 1995

• NIH Grant R01CA039961

  NIH · $617k · 1988

Frequent coauthors

• Roberto A. Gaxiola

  Arizona State University

  95 shared

• Paula Grisafi

  69 shared

• Cora A. Styles

  Whitehead Institute for Biomedical Research

  62 shared

• Jef D. Boeke

  Institute for Systems Biology

  52 shared

• Seth L. Alper

  Massachusetts Institute of Technology

  50 shared

• David P. Bartel

  Whitehead Institute for Biomedical Research

  48 shared

• Richard D. Klausner

  36 shared

• Daniel Yuan

  36 shared

Awards & honors

• Thomas Hunt Morgan Medal, Genetics Society of America, 2020
• James R. Killian Jr. Faculty Achievement Award, 2018
• American Association for the Advancement of Science, Fellow,…
• Gruber International Prize in Genetics, 2010
• American Philosophical Society, 2003