- Postdoctoral Training Fellow to investigate the role of Arp2/3 complex isoforms in mouse development and tissue homoeostasis
Closing date and time:
- 13 June 2021 at 23:59
- This is a full-time fixed term position for 4 years on Crick terms and conditions of employment.
We seek a motivated and independent postdoctoral research fellow to join the Cellular Signalling and Cytoskeletal Function laboratory headed by Michael Way at the Francis Crick Institute to investigate to the role of Arp2/3 complex isoforms in mouse development and tissue homoeostasis. The position represents an exciting opportunity to be part of a collaborative ERC synergy grant with Carolyn Moores (Birkbeck, London) and Edgar Gomes (IMM, Lisbon) investigating the molecular, cellular and physiological diversity of the Arp2/3 complex. The project will involve close interactions and visits between all three groups to achieve our ambitious goals. The successful candidate will be expected to drive their own independent research programme taking full advantage of our available conditional mouse models as well as generating new models and lines to investigate the developmental and physiological function of Arp2/3 isoforms. Applicants should have a PhD with a developmental background and experience working with mice.
The Arp2/3 complex consisting of seven subunits (Arp2, Arp3 and ARPC1–5) is conserved from yeast to man and plays an essential role in generating branched actin filament networks during a wide variety of fundamental cellular processes. Loss of Arp2/3 function is lethal. Interestingly, in humans and other mammals, Arp3, ARPC1 and ARPC5 exist as two different isoforms (Arp3/Arp3B, ARPC1A/ARPC1B and ARPC5/ARPC5L) that are 91, 67 and 67% identical respectively. The presence of these subunit isoforms suggests that the mammalian Arp2/3 complex is actually a family of 8 iso-complexes with different properties that are suited to particular cellular or physiological functions.
We previously demonstrated that ARPC1 and ARPC5 isoforms confer different actin nucleating properties to the Arp2/3 complex (Abella 2016, PMID:26655834). More recently, we established that Arp3 and Arp3B also impart different cellular properties to the Arp2/3 complex (Galloni 2020 doi: https://doi.org/10.1101/2020.09.21.306522). In addition, in collaboration, with Edgar Gomes (IMM, Lisbon), we have uncovered that the ARPC5 isoforms play unique roles in T-tubule organization and nuclei positioning in skeletal muscle (Roman 2017, PMID:28892082). The importance of Arp2/3 isoforms in tissue homeostasis is also underscored by the finding that loss of function mutations in ARPC1B lead to Wiskott-Aldrich syndrome like symptoms including severe inflammation and immunodeficiency as well as impaired cytotoxic T lymphocyte maintenance and cytolytic activity (Kahr 2017 PMID:28368018 and Randzavola 2019, PMID:31710310).
The task ahead is to investigate whether different Arp2/3 family members have differing developmental and physiological functions. The proposed project is part of a wider ERC funded synergy grant with Carolyn Moores, Birkbeck College, London and Edgar Gomes IMM, Lisbon, Portugal to understand the role of Arp2/3 complex diversity at three hierarchies of biology (molecular, cellular and physiological). The project will take advantage of a series of conditional mouse lines generated in the Way lab to investigate the role of the different Arp2/3 complexes in mouse development and tissue homeostasis. The specific question and long-term focus of the project will depend on results obtained from the initial characterization of mice, which have already identified cardiovascular and neural tube defects at E9-10 as well as the candidates own interests.
Details of current research projects and lab members can be seen at: (https://michaelway0.wixsite.com/waylab).
Key experience and competencies
Postdoctoral Training 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.
The post holder should embody and demonstrate our core Crick values: bold, imaginative, open, dynamic and collegial, in addition to the following:
- PhD in developmental biology
- Good knowledge of mouse development and experience working with mice
- Technical expertise in imaging and generation of mouse lines
- Track record of writing papers as evidenced by publications or preprints
- Evidence of data presentation at scientific meetings
- Ability to work independently and also capable of interacting within a group
- Experience in intravital imaging