Defining the role of myosin motor proteins and their cargo adaptors in cytokine secretion
Award Number
BB/R001316/1Status / Stage
CompletedDates
1 January 2018 -28 January 2023
Duration (calculated)
05 years 00 monthsFunder(s)
BBSRC (UKRI)Funding Amount
£370,698.00Funder/Grant study page
BBSRC UKRIContracted Centre
University of CambridgePrincipal Investigator
Professor Folma BussPI Contact
fb207@cam.ac.ukPI ORCID
0000-0003-4457-3479WHO Catergories
Understanding Underlying DiseaseDisease Type
Dementia (Unspecified)CPEC Review Info
| Reference ID | 673 |
|---|---|
| Researcher | Reside Team |
| Published | 07/07/2023 |
Data
| Award Number | BB/R001316/1 |
|---|---|
| Status / Stage | Completed |
| Start Date | 20180101 |
| End Date | 20230128 |
| Duration (calculated) | 05 years 00 months |
| Funder/Grant study page | BBSRC UKRI |
| Contracted Centre | University of Cambridge |
| Funding Amount | £370,698.00 |
Abstract
Cytokines are essential messengers that regulate innate and adaptive immunity. Although cytokine secretion by epithelial and immune cells is a fundamental process, we have only very rudimentary understanding how cytokines are transported, sorted and released from cells. Human aging is characterized by chronic, low-grade systemic inflammation with elevated levels of inflammatory cytokines. Thus treatments to correct age-dependent dysregulation of innate immunity may open new ways to support healthy ageing. In addition, the modulation of cytokine secretion can also induce the clearance of existing bacterial infections through activation of innate immunity. In this proposal we aim to identify the machinery especially the myosin motor proteins that mediate and regulate secretion of different cytokines from human cells. We have extensive experience in the study of myosin motor proteins in intracellular trafficking and protein secretion. We will utilise our knowledge and experience in advanced proteomics and in situ proximity labelling, high-resolution microscopy and cutting-edge cell biology techniques to identify the full repertoire of myosin motors that drive cytokine secretion and to establish the exact function of the different myosins along the exocytic pathway. Finally, we aim to develop inhibitors to target the different classes of myosin motors with roles in cytokine secretion. Our aims are: ->To identify and characterise the myosins with roles in cytokine secretion ->To characterise myosin-associated machinery that mediates cytokine release ->To established the exact role of different myosin-adaptor protein complexes in cytokine release ->To test existing myosin inhibitors and to develop new inhibitors for additional myosin classes This project will provide fundamental and import
Aims
In this proposal we aim to identify the machinery especially the myosin motor proteins that mediate and regulate secretion of different cytokines from human cells.