Why Patients Need You

Pfizer’s purpose is to deliver breakthroughs that change patients’ lives. Research and Development is at the heart of fulfilling Pfizer’s purpose as we work to translate advanced science and technologies into the therapies and vaccines that matter most. Whether you are in the discovery sciences, ensuring drug safety and efficacy or supporting clinical trials, you will apply cutting edge design and process development capabilities to accelerate and bring the best in class medicines to patients around the world.

What You Will Achieve

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 KAT 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 the enzymatic and structural characterization of MYST family KAT complexes.

How You Will Achieve It

• 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 your scientific hypothesis and experimental plan
• Effectively communicate data and results at internal and external meetings/conferences
• Bring expertise in enzymology, molecular and structural biology and an interest in epigenetics and KAT enzyme function
• Produce high impact publications in peer reviewed journals

Qualifications

Must-Have

• Recent Ph.D. in enzymology or biochemistry.
• Significant experience in functional characterization of enzyme activity, specificity and regulation.
• Extensive experience using enzyme kinetics to understand enzyme function.
• 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

Nice-to-Have

• Experience purifying proteins and protein complexes.
• Structural biology experience or experience with other biophysical methods for characterizing proteins (MS, ITC, SPR, AUC).

PHYSICAL/MENTAL REQUIREMENTS

Must be physically able to perform experiments at the bench, including light lifting, sitting, standing, walking, bending. Must have a strong understanding of mathematics, the ability to perform mathematical calculations including fitting data to complex equations, and ability to perform complex data analysis.

NON-STANDARD WORK SCHEDULE, TRAVEL OR ENVIRONMENT REQUIREMENTS

Must be vaccinated for COVID-19 or be willing to take weekly COVID tests.

Relocation support available

Research and Development#LI-PFE