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CEEHRC / Postdoctoral Fellow /

Two Postdoctoral Fellow Positions

Biochemistry and Cell Biology Focus

Molecular Mechanisms of MYST family of Acetyltransferases

ROLE SUMMARY

Pfizer Oncology R&D is working to change the trajectory of cancer by translating breakthrough discoveries in cancer research into the best medicines imaginable for cancer patients. The Epigenetics and Biochemistry and Quantitative Pharmacology groups have two postdoctoral positions available for highly- motivated candidates with expertise in enzymology, structural biology, biochemistry, cell and systems biology. Based in La Jolla, California, these scientists will work collaboratively to leverage unprecedented chemical and biological discovery platforms to further our understanding of lysine acetylation biology.

Genomic DNA is organized in the cell in repeating nucleosomal units which are further compacted into dense arrays. Chromatin structure is dynamic and directly related to gene expression. Chromatin structure is influenced, in part, by multiple modifications that exist on histone proteins, including methylation and acetylation of lysine residues within the histone tails. Lysine acetylation neutralizes the positive charge on histones and serves to physically relax chromatin, which increases accessibility to allow proteins involved in DNA transcription, replication, or repair to physically access the genome and execute their functions. Thus, lysine acetyltransferases (KATs) perform important regulatory functions and consequently, in cancers they are frequently targeted by mutations, translocations, and amplifications. The dysregulation of these enzymes can result in global changes in histone acetylation patterns, as well as gene-specific changes leading to altered transcription of oncogenes or tumor suppressor genes.

KATs are known to work in the context of large protein complexes. The Postdoctoral fellows will seek to better understand the function, specificity and regulation of these various KAT complexes and the impact of cancer associated KAT genetic alterations on their function. A foundation for this work will be characterization of relevant HAT complexes using a comprehensive platform of enzymatic characterization of KAT complexes, structural biology, cellular biology, CRISPR gene editing technology, and medicinal chemistry resources. This position will be focused on identifying the functional impact and cross-talk between various members of MYST family KAT complexes.

ROLE RESPONSIBILITIES (CELL BIOLOGY FOCUS)

  • Apply genetic and pharmacological approaches to modulate protein expression and function to assess impacts on protein acetylation, composition of KAT complexes, and gene regulation.

  • Work independently and collaboratively to conceive, design, execute, analyze/interpret, and refine experiments ranging from biochemical and molecular assays, epigenomics techniques such as ChIP- seq, RNA-seq, ATAC-seq, and proteomics approaches.

  • Independently, but with guidance by experienced mentors, develop results into compelling stories for publication in major scientific journals and presentations on major scientific meetings and conferences, both internally and externally.

  • Specific duties to include: CRISPR/CAS9 editing, RNAi, viral vector delivery, transfection, antibodies, small molecules and other pharmacologic approaches, and stable cell line generation.

  • Collaborate with groups to perform and analyze data including ChIP-seq, RNA-seq, ATAC-seq to support mechanism of action studies.

  • Execute secondary assays across various technology platforms – qRT-PCR, immunoprecipitation, ChIP-seq, ATAC-seq, FACS, immunofluorescence, western blotting, ELISA, high content imaging.

  • Use electronic data capture/analysis tools such as Excel, GraphPad, Biobook, Spotfire and PowerPoint for experimental documentation and data analysis/presentations.

  • Present research results and methodologies at weekly meetings with immediate supervisor and/or project leader, and at meetings with members of the oncology research unit as appropriate.

  • Contribute to building a culture that embraces scientific excellence, urgency, partnerships with key stakeholders, continuous learning and improvement, increasing technical skill base and cancer biology expertise; take a proactive role in personal growth and scientific development.

BASIC QUALIFICATIONS (CELL BIOLOGY FOCUS)

  • Ph.D. in biomedical sciences with focus on cancer Cell Biology, Molecular Biology, or Biochemistry (or a comparable biological science) with a track record of scientific accomplishment as exemplified by first author scientific publications.

  • Experience in nucleic acid and protein techniques and downstream analyses including quantitative RT-PCR, immunoprecipitation (including ChIP), CRISPR/CAS9, and immunoblotting.

  • Experience with computational tools for epigenomic data analysis is desired.

  • Ability to work in a team environment; excellent written and oral communication skills in English; strong presentation skills and ability to discuss data at project team meetings.

  • Excellent organizational skills, willingness to learn new skills, and demonstrated ability to work effectively as part of a team.

ROLE RESPONSIBILITIES (BIOCHEMISTRY FOCUS)

  • Enzymatically characterize various MYST Family KAT complexes with the goal of better understanding the molecular determinants of specificity and function.

  • Collaborate closely with the cell biology postdoc, structural biologists and other Pfizer scientists to explore fundamental research questions with an emphasis on novel discoveries that will result in high impact publications.

  • Participate in design of targeted experiments to address key questions on the molecular interactions and function of canonical and non-conical KAT complexes.

  • Organize, interpret, and analyze data, and identify areas where key knowledge is lacking.

  • Proactively seek out new information in the literature and incorporate this into their scientific hypothesis and experimental plan.

  • Effectively communicate data and results at internal and external meetings/conferences.

  • Expertise in enzymology, molecular and structural biology and an interest in epigenetics and KAT enzyme function.

  • Produce high impact publications in peer reviewed journals.

BASIC QUALIFICATIONS (BIOCHEMISTRY FOCUS)

  • Recent Ph.D. in enzymology, biochemistry or structural biology.

  • Significant experience in functional characterization of enzyme activity, specificity and regulation. Extensive experience using enzyme kinetics to understand enzyme function. Protein purification and structural biology experience or experience with biophysical methods (MS, ITC, SPR, AUC) a plus.

  • Excellent communication and organizational skills, willingness to learn new skills, and demonstrated ability to work effectively as part of a team.

  • Demonstrated research productivity by first-author publications in peer-reviewed journals.

HOW TO APPLY

Qualified candidates should submit their CV and cover letter to natalie.nady@pfizer.com (Cell Biology focus) or karen.maegley@pfizer.com (Biochemistry focus).

Location:
Pfizer - Oncology, La Jolla
Date posted: