Description

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Postdoctoral Fellow

Reporting to:Kate Bishop, Principal Group Leader

Contract term:This is a full-time, fixed term (4 years) position on Crick terms and conditions of employment.

Summary

Many retroviruses have accessory proteins. These are dispensable for viral replication in cell culture but are required , and often increase transmission or pathogenicity in the host. In recent years, it has become clear that the function of retroviral accessory proteins is to block cellular proteins that interfere with viral replication. Therefore, studying viral accessory proteins not only allows us to discover more about how the virus replicates, but also to learn more about cellular defence mechanisms and general cell biology.

Viral protein R (Vpr) is a 14-16 kDa accessory protein found in primate lentiviruses like HIV-1, that is actively packaged into viral particles, and is thus present during both early and late stages of infection. Vpr is a paralogue of Vpx, an accessory protein found in HIV-2, that targets the cellular SAMHD1 protein for degradation. Like Vpx, Vpr also interacts with the DDB1/CUL4A/ROC1 E3 ubiquitin ligase complex through an interaction with the substrate-adaptor protein DCAF and degrades cellular proteins. Various targets for Vpr have been reported, however, the role of Vpr during HIV infection is still currently unknown. Numerous effects of Vpr on the cell have been reported over the years, including disruption of cell cycle control, enhancement of transcription, and induction of both DNA damage and apoptosis. Recently, Vpr has also been linked to antagonising the silencing of integrated HIV-1 DNA that results in the viral reservoir in patients and is the main barrier to finding a cure for HIV.

The successful applicant will investigate the function and cellular targets of Vpr during HIV-1 replication, focusing initially on Vpr-induced DNA damage and how this promotes viral replication.

The Research Group

Retroviruses cause severe diseases including AIDS and cancer. Many anti-retroviral dugs and cellular anti-viral factors target the early stages of the viral life cycle. However, numerous events that occur during these stages are still poorly understood. Dr Bishop’s laboratory focuses on the early, post-entry replication of retroviruses including HIV and MLV. She is interested in understanding the molecular events that occur when a retrovirus infects its target cell in order to fully understand retroviral replication and provide potential ways in which to manipulate these processes for the benfit of human health. Details of current research projects can be seen at: . Her lab uses a wide range of research techniques including virological, biochemical and microscopy techniques and she collaborates closely with structural biologists.

The Role

Dr Bishop is seeking a talented and motivated postdoc to study the function of the HIV Vpr protein during HIV infection.

The successful applicant will investigate how Vpr impacts the cell and how this promotes viral replication. The project will initially focus on Vpr-induced DNA damage and the effects on chromatin, but all aspects of Vpr biology may be investigated.

Postdoctoral Fellows are expected to lead their own projects, contribute to other projects on a collaborative basis (both in the lab and with external collaborators) and guide PhD students in their research. The ability to work in a team is essential.

Key experience and competencies

The post holder should embody and demonstrate our core Crick values: bold, imaginative, open, dynamic and collegial, in addition to the following:

Essential

PhD in virology, cell biology or molecular biology Good knowledge and understanding of retrovirology Expertise in molecular biology and biochemical techniques Expertise in cell culture and transfection Pro-active in innovation and problem solving Experience of experimental design Track record of writing papers as evidenced by publications or submitted manuscripts in referred journals Evidence of data presentation at scientific meetings Ability to work independently and also capable of interacting within a group

Desirable

Experience working with primary cells Experience in microscopy Experience in flow cytometry Good understanding of bioinformatics Research experience of DNA damage pathways Research experience of viral accessory proteins or innate immunity

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Equality, Diversity & Inclusion:

We welcome applications from all backgrounds. We are committed to providing equal employment opportunities, regardless of ethnicity, nationality, gender, sexual orientation, gender identity, religion, pregnancy, age, disability, or civil partnership, marital or family status. We particularly welcome applications from people who are Minority Ethnic as they are currently underrepresented in the Crick at this level.

Diversity is essential to excellence in scientific endeavour. It increases breadth and perspective, leading to more innovation and creativity. We want the Crick to be a place where everyone feels valued and where diversity is celebrated and seen as part of the foundation for our Institute’s success.

The Crick is committed to creating equality of opportunity and promoting diversity and inclusivity. We all share in the responsibility to actively promote dignity, respect, inclusivity and equal treatment and it is our aim to ensure that these principles are reflected and implemented in all strategies, policies and practices.

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