About

Andrew Murray grew up in England with American parents and was inspired to become a scientist by his high school chemistry teacher, "Doc" Powell, after realizing that his initial ambition to be a race car driver was not feasible due to his slow reflexes. He completed his Ph.D. with Jack Szostak, where he worked on constructing artificial chromosomes, and conducted postdoctoral research with Mark Kirschner, demonstrating that cyclin synthesis and destruction regulate the cell division cycle. His research group focuses on experimental evolution using the brewer's yeast, Saccharomyces cerevisiae. They employ genetic and physiological perturbations, synthetic biology, and collaborations with theorists to understand the "rules of the game" that explain how cells reproduce, respond to their environment, and evolve. The Murray Lab investigates fundamental questions about cellular function and evolution by studying budding yeast through experimental evolution, genetic analysis, synthetic biology, and cell biology. Their work includes evolving multicellularity, altering mating preferences, circadian oscillators, genetic instability, and new connections between signaling pathways. They develop methods to identify mutations responsible for new phenotypes and explore both general evolutionary trajectories and specific mechanisms organisms use to produce novel traits. The lab also studies how cells accomplish specific tasks and how these solutions evolved, applying the Feynman principle, "What I cannot create, I cannot understand," by engineering and analyzing new yeast strains. Their synthetic biology work supports ideas such as the efficient use of secreted public goods driving the evolution of multicellularity, multicellularity arising before cellular differentiation, and the emergence of novel symbioses without prior evolutionary co-adaptation. Additionally, the lab examines how yeast cells respond and adapt to environmental changes to maximize survival and reproduction. They have discovered that yeast can rapidly halt their cell cycles at any stage in response to sudden starvation and later resume cell division slowly. Their research addresses how cells arrest, whether this arrest destabilizes the genome, and how cells adapt to restart division. Andrew Murray is also interested in education, particularly in breaking interdisciplinary barriers without sacrificing disciplinary depth.

Research topics

• Biology
• Evolutionary biology
• Genetics
• Computational biology
• Biochemistry
• Cell biology
• Botany

Selected publications

• Competition between mitochondrial and cytosolic ribosomes produces a bistable metabolic switch

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-03-31

  articleOpen accessSenior authorCorresponding

  Abstract Fast glycolytic growth in the budding yeast, Saccharomyces cerevisiae , produces two epigenetic states 1 : arrestors, which primarily ferment, and recoverers, which respire. Positive feedback in mitochondrial translation produces the two states: mitochondrial membrane potential drives the import of positively charged nuclear-encoded proteins of the mitochondrial ribosome and mitochondrial ribosomes produce key electron transport chain subunits, sustaining the membrane potential and completing the positive feedback loop. The co-operative incorporation of three mitochondrially encoded and translated subunits of respiratory complex IV converts the positive feedback to a bistable switch. A single effective parameter determines bistability: the rate of mitochondrial protein synthesis, which produces complex IV, relative to the rate of cytoplasmic protein synthesis, which sets the rate of cell growth thus diluting mitochondrially synthesized proteins. Slowing mitochondrial protein synthesis increases the fraction of arrestors and slowing cytoplasmic protein synthesis opposes it. Reducing mitochondrial protein synthesis reconstitutes bistability in the evolutionary distant fission yeast suggesting a conserved, bistable switch enabling transitions between two metabolic strategies.

  PublisherDOI

• The B-type cyclin Clb4 prevents meiosis I sister centromere separation in budding yeast

  G3 Genes Genomes Genetics · 2025-05-30 · 1 citations

  articleOpen accessSenior author

  In meiosis, one round of DNA replication followed by two rounds of chromosome segregation halves the ploidy of the original cell. Accurate chromosome segregation in meiosis I depends on recombination between homologous chromosomes. Sister centromeres attach to the same spindle pole in this division and only segregate in meiosis II. We used budding yeast to select for mutations that produced viable spores in the absence of recombination. The most frequent mutations inactivated CLB4, which encodes one of four B-type cyclins. In two wild yeast isolates, Y55 and SK1, but not the W303 laboratory strain, deleting CLB4 causes premature sister centromere separation and segregation in meiosis I and frequent termination of meiosis after a single division, demonstrating a novel role for Clb4 in meiotic chromosome dynamics and meiotic progression. This role depends on the genetic background since meiosis in W303 is largely independent of CLB4.

  PublisherOA PDFDOI

• Cell integrity limits ploidy in budding yeast

  G3 Genes Genomes Genetics · 2025-01-13 · 2 citations

  articleOpen access

  Evidence suggests that increases in ploidy have occurred frequently in the evolutionary history of organisms and can serve adaptive functions to specialized somatic cells in multicellular organisms. However, the sudden multiplication of all chromosome content may present physiological challenges to the cells in which it occurs. Experimental studies have associated increases in ploidy with reduced cell survival and proliferation. To understand the physiological challenges that suddenly increased chromosome content imposes on cells, we used S. cerevisiae to ask how much chromosomal DNA cells may contain and what determines this limit. We generated polyploid cells using 2 distinct methods causing cells to undergo endoreplication and identified the maximum ploidy of these cells, 32-64C. We found that physical determinants that alleviate or exacerbate cell surface stress increase and decrease the limit to ploidy, respectively. We also used these cells to investigate gene expression changes associated with increased ploidy and identified the repression of genes involved in ergosterol biosynthesis. We propose that ploidy is inherently limited by the impacts of growth in size, which accompany whole-genome duplication, to cell surface integrity.

  PublisherOA PDFDOI

• A ribosome-associating chaperone mediates GTP-driven vectorial folding of nascent eEF1A

  Nature Communications · 2025-02-03 · 6 citations

  articleOpen access

  Eukaryotic translation elongation factor 1A (eEF1A) is a highly abundant, multi-domain GTPase. Post-translational steps essential for eEF1A biogenesis are carried out by bespoke chaperones but co-translational mechanisms tailored to eEF1A folding remain unexplored. Here, we use AlphaPulldown to identify Ypl225w (also known as Chp1, Chaperone 1 for eEF1A) as a conserved yeast protein predicted to stabilize the N-terminal, GTP-binding (G) domain of eEF1A against its misfolding propensity, as predicted by computational simulations and validated by microscopy analysis of ypl225wΔ cells. Proteomics and biochemical reconstitution reveal that Ypl225w functions as a co-translational chaperone by forming dual interactions with the eEF1A G domain nascent chain and the UBA domain of ribosome-bound nascent polypeptide-associated complex (NAC). Lastly, we show that Ypl225w primes eEF1A nascent chains for binding to GTP as part of a folding mechanism tightly coupled to chaperone recycling. Our work shows that an ATP-independent chaperone can drive vectorial folding of nascent chains by co-opting G protein nucleotide binding. Folding of abundant, complex proteins can begin during their synthesis. Here, Sabbarini et al. show that the conserved protein Ypl225w (Chp1) functions as a co-translational chaperone for eEF1A and identify a role for NAC in the process as a recruitment factor.

  PublisherOA PDFDOI

• The B-type cyclin Clb4 prevents meiosis I sister centromere separation in budding yeast

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-12-19

  preprintOpen accessSenior authorCorresponding

  Abstract In meiosis, one round of DNA replication followed by two rounds of chromosome segregation halves the ploidy of the original cell. Accurate chromosome segregation in meiosis I depends on recombination between homologous chromosomes. Sister centromeres attach to the same spindle pole in this division and only segregate in meiosis II. We used budding yeast to select for mutations that produced viable spores in the absence of recombination. The most frequent mutations inactivated CLB4 , which encodes one of four B-type cyclins. In two wild yeast isolates, Y55 and SK1, but not the W303 laboratory strain, deleting CLB4 causes premature sister centromere separation and segregation in meiosis I and frequent termination of meiosis after a single division, demonstrating a novel role for Clb4 in meiotic chromosome dynamics and meiotic progression. This role depends on the genetic background since meiosis in W303 is largely independent of CLB4 .

  PublisherDOI

• A ribosome-associating chaperone mediates GTP-driven vectorial folding of nascent eEF1A

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-02-22

  preprintOpen access

  Abstract Eukaryotic translation elongation factor 1A (eEF1A) is a highly abundant, multi-domain GTPase. Post-translational steps essential for eEF1A biogenesis are carried out by bespoke chaperones but co-translational mechanisms tailored to eEF1A folding remain unexplored. Here, we find that the N-terminal, GTP-binding domain of eEF1A is prone to co-translational misfolding and using computational approaches, yeast genetics, and microscopy analysis, we identify the conserved yet uncharacterized yeast protein Ypl225w as a chaperone dedicated to solving this problem. Proteomics and biochemical reconstitution reveal that Ypl225w’s interaction with ribosomal eEF1A nascent chains depends on additional binding of Ypl225w to the UBA domain of nascent polypeptide-associated complex (NAC). Lastly, we show by orthogonal chemical genetics that Ypl225w primes eEF1A nascent chains for their subsequent binding to GTP and release from Ypl225w. Our work establishes eEF1A as a model system for chaperone-dependent co-translational folding and unveils a novel mechanism for GTP-driven folding on the ribosome.

  PublisherOA PDFDOI

• Alternating selection for dispersal and multicellularity favors regulated life cycles

  Current Biology · 2024-03-01 · 1 citations

  erratumOpen accessSenior author
  PublisherOA PDFDOI

• A dynamic network model predicts the phenotypes of multicellular clusters from cellular properties

  Current Biology · 2024-05-31 · 4 citations

  articleOpen accessSenior authorCorresponding
  PublisherOA PDFDOI

• Smar2C2: A Simple and Efficient Protocol for the Identification of Transcription Start Sites

  Current Protocols · 2023-03-01 · 2 citations

  articleOpen access1st author

  Promoters and the noncoding sequences that drive their function are fundamental aspects of genes that are critical to their regulation. The transcription preinitiation complex binds and assembles on promoters where it facilitates transcription. The transcription start site (TSS) is located downstream of the promoter sequence and is defined as the location in the genome where polymerase begins transcribing DNA into RNA. Knowing the location of TSSs is useful for annotation of genes, identification of non-coding sequences important to gene regulation, detection of alternative TSSs, and understanding of 5' UTR content. Several existing techniques make it possible to accurately identify TSSs, but are often difficult to perform experimentally, require large amounts of input RNA, or are unable to identify a large number of TSSs from a single sample. Many of these protocols take advantage of template switching reverse transcriptases (TSRTs), which reliably place an adaptor at the 5' end of a first strand synthesis of cDNA. Here, we introduce a protocol that exploits TSRT activity combined with rolling circle amplification to identify TSSs with several unique advantages over existing methods. Sequence adaptors are placed on the 5' and 3' end of the full-length cDNA copy of a transcript. A splint compatible with those adaptors is then used to circularize the full-length cDNA. Linear DNA containing concatemers of the cDNA are generated using rolling circle amplification, and a sequencing library is formed by fragmenting the concatemers. This protocol is straightforward to execute, requiring limited bench time with relatively stable reagents. Using extremely low amounts of RNA input, this protocol produces large numbers of accurate, deduplicated TSSs genome wide. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Splint generation Basic Protocol 2: RNA extraction Basic Protocol 3: cDNA synthesis Basic Protocol 4: cDNA circularization and amplification Basic Protocol 5: Library generation.

  PublisherOA PDFDOI

• Extending the reach of homology by using successive computational filters to find yeast pheromone genes

  Current Biology · 2023-09-11 · 5 citations

  articleOpen accessSenior authorCorresponding
  PublisherOA PDFDOI

Recent grants

• NSF-Simons Center for Mathematical and Statistical Analysis of Biology

  NSF · $5.0M · 2018–2024

• Feedback Control of the Cell Cycle

  NIH · $8.4M · 1990–2025

• NIH Grant R37GM043987

  NIH · $4.9M · 2010

• NIH Grant P50GM068763

  NIH · $24.4M · 2014

Frequent coauthors

• David R. Nelson

  43 shared

• Jack W. Szostak

  40 shared

• Rey‐Huei Chen

  Institute of Molecular Biology, Academia Sinica

  26 shared

• John H. Koschwanez

  19 shared

• Antonio Ferrante

  South Australia Pathology

  18 shared

• Lauren A. O’Connell

  Stanford University

  16 shared

• Joshua B. Plotkin

  University of Pennsylvania

  16 shared

• Charles S. Hii

  Women's and Children's Hospital

  16 shared

Education

• Cell and Developmental Biologhy, Division of Medical Sciences

  Harvard Medical School

  1984

• Biochemistry, Natural Sciences

  Clare College, University of Cambridge

  1978