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Postdoc Fellow – Lysosome Targeting Chimeras

Location Waltham, Massachusetts, United States Job ID R-076768 Date posted 03/25/2020

About the Opportunity:

We have an exciting opportunity to join the Chemical Biology team at AstraZeneca and discover new ways of modulating protein functions contributing to the evolving protein degradation field

This role will join our Discovery Sciences department, which was established in 2011 as a scientific unit that works across all disease areas, modalities, and geographic locations in supporting the identification of quality targets, hits, leads, and drug candidates.

As a postdoctoral scientist in the Discovery Sciences - Chemical Biology and Proteomics department, you will address critical problems in drug discovery and collaborate with top academic and industrial scientists in small molecule and biologics-based therapeutics. You will train with the top chemical biology and proteomics group in the industry, while simultaneously gaining exposure to different therapeutic areas such as Oncology, respiratory and Inflammation and Cardiovascular. Our program provides a unique blended academic and industrial intellectual environment; this unparalleled opportunity provides the potential for high impact publications, and serves a great launchpad for a career in academia or industry.

Key Accountabilities:

  • Design and synthesis of chemical probes
  • Proof-of-concept for application of small molecule-lysosome targeting chimeras for degradation of extracellular proteins.
  • Develop biochemical and cellular assays that measure the binding affinity of target ligands and chimeras to their intended targets.
  • Develop and apply cellular imaging assays to monitor protein internalization
  • Full characterization of developed degraders via proteomics approaches, to determine selectivity of binding/degradation and protein turnover rates
  • Protein reagents/binding assay can be accessed through the internal project
  • Collaborate with internal and external scientists from multiple different backgrounds as project requires.
  • Present results at AstraZeneca symposia, external scientific conferences, and publish peer-reviewed scientific papers in high quality journals.

Essential Education and Experience:

  • PhD in Chemical Biology, Chemistry, or Biochemistry
  • Experience in the design and synthesis of chemical probes
  • Proficient in mammalian cell culture, including the design, execution, and analysis of results from complex biochemical and cellular assays, including imaging-based assays
  • Strong organizational, communication (oral and written), and interpersonal skills
  • Proven record of work published in reputable scientific journals
  • Demonstrated leadership skills with experience and passion to summarize data in peer reviewed publications and reviews
  • Ability to multitask and confidence in conducting research at the interface of chemistry and biology

Desirable Qualifications:

  • Awareness of recent developments in in the fields of chemical biology, and/or proteomics, and/or ubiquitin proteasome biology
  • Experience in labeling of small molecules/peptides with fluorophores for imaging of subcellular localization and trafficking
  • Previous and current activity in Chemical Biology forums and a strong publication record in the field (communications at symposia, peer reviewed journal articles, and/or patent applications)

Skills and Capabilities required:

  • Familiarity with chemical biology principles and technologies, and their application to understand how small molecules affect complex biological systems
  • The ideal candidate will have knowledge of ubiquitin proteasome biology and protein degradation approaches (e.g. PROTACS)
  • Independently design and execute experiments for generation of chemical probes.
  • Independently design and execute assays for interrogation of cellular signalling pathways
  • Practical knowledge of suitable biological models for hypothesis testing with emphasis on positive and negative control experiments using small molecules.

About AstraZeneca

AstraZeneca is a global, innovation-driven biopharmaceutical business that focuses on the discovery, development and commercialization of prescription medicines for some of the world’s most serious diseases. But we're more than one of the world's leading pharmaceutical companies. At AstraZeneca, we're proud to have a unique workplace culture that inspires innovation and collaboration. Here, employees are empowered to express diverse perspectives - and are made to feel valued, energized and rewarded for their ideas and creativity.

Advert opening date: March 26, 2020

Advert closing date: May 21, 2020

AstraZeneca embraces diversity and equality of opportunity. We are committed to building an inclusive and diverse team representing all backgrounds, with as wide a range of perspectives as possible, and harnessing industry-leading skills. We believe that the more inclusive we are, the better our work will be. We welcome and consider applications to join our team from all qualified candidates, regardless of their characteristics. We comply with all applicable laws and regulations on non-discrimination in employment (and recruitment), as well as work authorisation and employment eligibility verification requirements.

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