Job Number: 155410528
Company Name: AstraZeneca Pharmaceuticals LP
Location: Waltham, MA
Career Focus: Science & Biotech
Position Title: Building fundamental mechanistic insights into factors leading to productive cell uptake and target inhibition by antisense oligonucleotides
At AstraZeneca We are seeking talented scientists who are interested in pursuing an academic-style Postdoc in a global pharmaceutical setting and contributing to AstraZeneca”s commitment to delivering innovative medicines. This newly expanded internal pharmaceutical Postdoctoral research program spans multiple therapeutic areas and a wide range of scientific disciplines.
Your comprehensive training program includes a focus on drug discovery and development, as well as exposure to existing local and global Postdoctoral Research communities within AstraZeneca. Postdoctoral scientists will have the opportunity to conduct independent cutting-edge work in state-of-the-art laboratories while teaming with other AstraZeneca scientists.
Each Postdoctoral scientist will also be able to collaborate with a leading academic advisor who will provide further support and guidance. Additionally, the Postdoc will be encouraged to attend and present at international scientific conferences and publish high-profile papers.
The aim of this project is to explore the contribution of specific tumor microenvironment factors to the productive uptake of antisense oligonucleotides (ASOs) into tumor cells, leading to effective target knockdown. The focus will be on diffuse large B-cell lymphoma (DLBCL), and gaining insight into two potential mechanisms that can drive the productive uptake and intracellular trafficking of ASOs: extracellular matrix interactions and macrophage-mediated exosomal delivery.
Successful execution of the project requires:
* Skill and expertise (some from graduate work, some to be gained during the postdoctoral research project) in the areas of:
1. extracellular matrix regulation of intracellular trafficking
2. state-of-the-art intracellular imaging techniques
3. macrophage function / exosome biology
* Working collaboratively with internal and external experts in these areas.
* Synthesis of findings in these areas to gain novel insights into mechanisms that control ASO uptake and trafficking, leading to target knockdown in tumor cells
Deliverables by the end of the project include:
* Novel findings that enhance the understanding of the mechanisms that drive cellular uptake and intracellular trafficking of ASOs
* Identification of the roles of specific proteins in tumor cells that could be expoited to improve uptake of ASOs, leading to improved target knockdown and activity
* Share progress with AstraZeneca collaborators in oligonucleotide therapeutic programs, including Isis and Regulus
* Minimum of one publication in a top tier, peer reviewed journal
* Presentation of findings at a major cancer, cell biology, or oligonucleotide focused international meeting
The results of this research have the potential to lead to therapeutic approaches that enhance productive uptake of ASOs, including the potential to direct the chemistry and design of oligonucleotides to maximize productive uptake for existing programs, and to enable selection of patients most likely to respond to ASO therapy.
Candidate Knowledge, Skills and Experience
Minimum experience and expertise:
* Recent PhD, with research focused in the areas of extracellular matrix interactions, intracellular trafficking, and/or macrophage biology in oncology
* Papers in one or more of the above areas published or accepted in peer-reviewed journals
* Expertise in cell biology techniques
* Ability to develop and test hypotheses based on observations from multiple disciplines
Additional desired (but not required) experience:
* Expertise with intracellular imaging techniques
* Experience with cellular models of lymphoma
* Experience with oligonucleotide therapeutics
This position will have regular interaction with scientists across the AstraZeneca organization, including individuals in pharmacology and bioscience, at multiple locations and at multiple levels, as well as external collaborators. The following abilities will be essential for success in this project:
* work cross-functionally
* seek out expertise from multiple sources
* manage advice and feedback from these sources
* strategic thinking and the ability to work independently to design and drive key experiments
* strong presentation and data reporting skills
Equal Opportunity Employer Minorities/Women/Protected Veterans/Disabled/Sexual Orientation
*Date Posted:* 04/30/2014
*Location:* Waltham, MA, USA
*Category:* Research and Non-Clinical Development