Relevant Degree Programs
Complete these steps before you reach out to a faculty member!
- Familiarize yourself with program requirements. You want to learn as much as possible from the information available to you before you reach out to a faculty member. Be sure to visit the graduate degree program listing and program-specific websites.
- Check whether the program requires you to seek commitment from a supervisor prior to submitting an application. For some programs this is an essential step while others match successful applicants with faculty members within the first year of study. This is either indicated in the program profile under "Requirements" or on the program website.
- Identify specific faculty members who are conducting research in your specific area of interest.
- Establish that your research interests align with the faculty member’s research interests.
- Read up on the faculty members in the program and the research being conducted in the department.
- Familiarize yourself with their work, read their recent publications and past theses/dissertations that they supervised. Be certain that their research is indeed what you are hoping to study.
- Compose an error-free and grammatically correct email addressed to your specifically targeted faculty member, and remember to use their correct titles.
- Do not send non-specific, mass emails to everyone in the department hoping for a match.
- Address the faculty members by name. Your contact should be genuine rather than generic.
- Include a brief outline of your academic background, why you are interested in working with the faculty member, and what experience you could bring to the department. The supervision enquiry form guides you with targeted questions. Ensure to craft compelling answers to these questions.
- Highlight your achievements and why you are a top student. Faculty members receive dozens of requests from prospective students and you may have less than 30 seconds to pique someone’s interest.
- Demonstrate that you are familiar with their research:
- Convey the specific ways you are a good fit for the program.
- Convey the specific ways the program/lab/faculty member is a good fit for the research you are interested in/already conducting.
- Be enthusiastic, but don’t overdo it.
G+PS regularly provides virtual sessions that focus on admission requirements and procedures and tips how to improve your application.
Great Supervisor Week Mentions
Here's to @pcstirling for supporting all of us, challenging us, and making us better scientists everyday!
Graduate Student Supervision
Doctoral Student Supervision (Jan 2008 - May 2019)
Chromosome instability (CIN) is characterized by an increased rate of the unequal distribution of DNA between daughter cells. Such changes in chromosome structure or number can occur due to both mitotic defects leading to aneuploidy and DNA damage-induced chromosome rearrangements. Previous large-scale screens for CIN genes in the model organism Saccharomyces cerevisiae identified DIS3, which encodes a catalytic component of the core RNA exosome complex, as a novel CIN gene. Mutations in human DIS3 have been identified in roughly 11% of multiple myeloma (MM) cases. I sought to recapitulate MM-associated point mutations at conserved sites in yeast cells, in order to understand the mechanism of emergent CIN in MM. I have found that MM-associated DIS3 exonuclease mutations do increase the frequency of CIN. A temperature sensitive DIS3 mutant accumulates DNA:RNA hybrids, however analysis of DNA damage foci by microscopy revealed no increase in double-strand breaks in any of the tested strains. Yeast DIS3 exonuclease mutants experience growth retardation, temperature sensitivity, and an altered cell cycle. Microarray analysis of one MM mutant has additionally demonstrated downregulation of cell cycle components, consistent with the potential for mitotic defects, in addition of upregulation of a host of metabolic pathways. Further, genetic interaction profiling by synthetic genetic array indicates MM-associated DIS3 mutations synthetically interact with rRNA processing proteins, as well as a host of mitotic regulators and metabolic pathways, particularly those involved in spindle and kinetochore function. Further, I verify that DIS3 mutants have a functional spindle assembly checkpoint, and are in fact resistant to microtubule poisons. Finally, I discover that the fitness defects induced by these mutations can be abrogated through culturing on media containing only a non-fermentable carbon source, suggesting that growth on poor carbon sources may also rescue CIN.Together, these results demonstrate extensive phenotypic consequences of MM-associated point mutations in DIS3, and support a model for CIN in DIS3 mutants involving defects in mitotic progression.
Master's Student Supervision (2010 - 2018)
Gene-gene or gene-drug interactions are typically quantified using fitness as a readout because the data is continuous and easily measured in high-throughput. However, to what extent fitness captures the range of other phenotypes that show synergistic effects is usually unknown. Using Saccharomyces cerevisiae, and focusing on a matrix of DNA repair mutants and genotoxic drugs, I quantified 76 gene-drug interactions based on both mutation rate and fitness and find that these parameters are not connected. Independent of fitness defects I identified seven cases of synthetic hypermutation, where the combined effect of the drug and mutant on mutation rate was greater than predicted. One example occurred when yeast lacking RAD1 were exposed to cisplatin and I characterized this interaction using whole-genome sequencing. Our sequencing results indicate mutagenesis by cisplatin in rad1∆ cells depended almost entirely on interstrand crosslinks at GpCpN motifs. Interestingly, our data suggest that the 3’ base in this motif templates the addition of the mutated base. This result differs from cisplatin mutation signatures in XPF-deficient C. elegans and supports a model in which translesion synthesis polymerases perform a slippage and realignment extension across from the damaged base. Accordingly, DNA polymerase zeta activity was essential for mutagenesis in cisplatin-treated rad1∆ cells. Together these data reveal the potential to gain new mechanistic insights from non-fitness measures of gene-drug interactions and extend the use of mutation accumulation and whole-genome sequencing analysis to define DNA repair mechanisms.
- Exonuclease domain mutants of yeast DIS3 display genome instability (2019)
Nucleus, 10 (1), 1-12
- Molecular characterization of an MLL1 fusion and its role in chromosomal instability (2019)
Molecular Oncology, 13 (2), 422-440
- MRE11-RAD50-NBS1 promotes Fanconi Anemia R-loop suppression at transcription–replication conflicts (2019)
Nature Communications, 10 (1)
- R Loops and Their Composite Cancer Connections (2019)
Trends in cancer,
- Selective defects in gene expression control genome instability in yeast splicing mutants (2019)
Molecular Biology of the Cell, 30 (2), 191-200
- Splicing, genome stability and disease: splice like your genome depends on it! (2019)
Current Genetics, 65 (4), 905-912
- Chromatin as a Platform for Modulating the Replication Stress Response (2018)
- The A-like faker assay for measuring yeast chromosome III stability (2018)
Methods in Molecular Biology, 1672, 1-9
- Canonical DNA Repair Pathways Influence R-Loop-Driven Genome Instability (2017)
Journal of Molecular Biology, 429 (21), 3132-3138
- CuboCube: Student creation of a cancer genetics e-textbook using open-access software for social learning (2017)
PLoS Biology, 15 (3)
- CX-5461 is a DNA G-quadruplex stabilizer with selective lethality in BRCA1/2 deficient tumours (2017)
Nature Communications, 8
- Genome-wide bisulfite sensitivity profiling of yeast suggests bisulfite inhibits transcription (2017)
Mutation Research - Genetic Toxicology and Environmental Mutagenesis, 821, 13-19
- Hypermutation signature reveals a slippage and realignment model of translesion synthesis by Rev3 polymerase in cisplatin-treated yeast (2017)
Proceedings of the National Academy of Sciences of the United States of America, 114 (10), 2663-2668
- RECQ-like helicases Sgs1 and BLM regulate R-loop- associated genome instabil (2017)
Journal of Cell Biology, 216 (12), 3991-4005
- Replication fork protection factors controlling R-loop bypass and suppression (2017)
Genes, 8 (1)
- Selective aggregation of the splicing factor Hsh155 suppresses splicing upon genotoxic stress (2017)
Journal of Cell Biology, 216 (12), 4027-4040
- Combined use of gene expression modeling and siRNA screening identifies genes and pathways which enhance the activity of cisplatin when added at no effect levels to non-small cell lung cancer cells in vitro (2016)
PLoS ONE, 11 (3)
- Dosage mutator genes in saccharomyces cerevisiae: A novel mutator mode-of-action of the Mph1 DNA helicase (2016)
Genetics, 204 (3), 975-986
- Navigating yeast genome maintenance with functional genomics (2016)
Briefings in Functional Genomics, 15 (2), 119-129
- 3′-Phosphoadenosine 5′-phosphosulfate synthase 1 (PAPSS1) knockdown sensitizes non-small cell lung cancer cells to DNA damaging agents (2015)
Oncotarget, 6 (19), 17161-17177
- An updated collection of sequence barcoded temperature-sensitive alleles of yeast essential genes (2015)
G3: Genes, Genomes, Genetics, 5 (9), 1879-1887
- Dissecting genetic and environmental mutation signatures with model organisms (2015)
Trends in Genetics, 31 (8), 465-474
- Erratum: Human prefoldin inhibits amyloid-β (Aβ) fibrillation and contributes to formation of nontoxic Aβ aggregates (Biochemistry (2013) 52:20 (3532-3542) DOI: 10.1021/bi301705c) (2014)
Biochemistry, 53 (21)
- Genome destabilizing mutator alleles drive specific mutational trajectories in Saccharomyces cerevisiae (2014)
Genetics, 196 (2), 403-412
- Genome-Wide Profiling of Yeast DNA:RNA Hybrid Prone Sites with DRIP-Chip (2014)
PLoS Genetics, 10 (4)
- Mechanisms of genome instability induced by RNA-processing defects (2014)
Trends in Genetics, 30 (6), 245-253
- Biogenesis of RNA polymerases II and III requires the conserved GPN small GTPases in Saccharomyces cerevisiae (2013)
Genetics, 193 (3), 853-864
- Human prefoldin inhibits amyloid-β (Aβ) fibrillation and contributes to formation of nontoxic Aβ aggregates (2013)
Biochemistry, 52 (20), 3532-3542
- Saccharomyces cerevisiae genetics predicts candidate therapeutic genetic interactions at the mammalian replication fork (2013)
G3: Genes, Genomes, Genetics, 3 (2), 273-282
- Mutability and mutational spectrum of chromosome transmission fidelity genes (2012)
Chromosoma, 121 (3), 263-275
- R-loop-mediated genome instability in mRNA cleavage and polyadenylation mutants (2012)
Genes and Development, 26 (2), 163-175
- The complete spectrum of yeast chromosome instability genes identifies candidate cin cancer genes and functional roles for astra complex components (2011)
PLoS Genetics, 7 (4)
- Quality control of cytoskeletal proteins and human disease (2010)
Trends in Biochemical Sciences, 35 (5), 288-297
- A Yeast Killer Toxin Screen Provides Insights into A/B Toxin Entry, Trafficking, and Killing Mechanisms (2009)
Developmental Cell, 17 (4), 552-560
- The interaction network of the chaperonin CCT (2008)
EMBO Journal, 27 (13), 1827-1839
- Divergent Substrate-Binding Mechanisms Reveal an Evolutionary Specialization of Eukaryotic Prefoldin Compared to Its Archaeal Counterpart (2007)
Structure, 15 (1), 101-110
- Functional interaction between phosducin-like protein 2 and cytosolic chaperonin is essential for cytoskeletal protein function and cell cycle progression (2007)
Molecular Biology of the Cell, 18 (6), 2336-2345
- Convergent evolution of clamp-like binding sites in diverse chaperones (2006)
Nature Structural and Molecular Biology, 13 (10), 865-870
- PhLP3 modulates CCT-mediated actin and tubulin folding via ternary complexes with substrates (2006)
Journal of Biological Chemistry, 281 (11), 7012-7021
- Molecular clamp mechanism of substrate binding by hydrophobic coiled-coil residues of the archaeal chaperone prefoldin (2004)
Proceedings of the National Academy of Sciences of the United States of America, 101 (13), 4367-4372
- Getting a grip on non-native proteins (2003)
EMBO Reports, 4 (6), 565-570