CLM RECEPTOR FAMILY · CMRF35-like molecules: a novel receptor family involved in the control of myeloid cell function
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2004-03-15 → 2006-03-14
- EU contribution
- €260,060
- Participants
- 1
- Scheme
- EIF
Lines connect the coordinator with its partners.
Results in brief
Final Activity Report Summary - CLM RECEPTOR FAMILY (CMRF35-like molecules: a novel receptor family involved in the control of myeloid cell function)
The work has involved the study of novel receptors expressed by the white blood cells of the immune system. Receptors are small protein molecules that are present on the surface of white blood cells that enable the cells to interact with their environment. For instance they may allow the cells to detect bacteria or viruses that are present in the body. Other receptors allow fine tuning of the cell activation state by activating or inhibiting cell processes. We have shown that one of the receptors that we are studying is an activating receptor that activates the killing process in one type of white blood cell, known as a natural killer cell. Natural killer cells kill infected or tumour cells found in the body. The next step is to determine what this receptor binds to (a structure known as the receptor ligand) so that we know what it helps the white blood cells to recognize. This is an extremely difficult task, but we have developed a very stable and sensitive system that allows us to do this. We have already used this system to identify the ligands for a number of receptors expressed by natural killer cells, and have begun to use it to hunt the ligands of the novel receptors that we are studying. We have identified cells that express the ligands on the cell surface and are in the process of identifying precisely what the ligands are.
Data: CORDIS, © European Union
Project objective
Cells of the myeloid lineage are the major cellular component of the innate immune system. They orchestrate the adaptive immune response and play a major role in inflammatory pathologies and tumour progression. Given these facts, a more thorough understanding of the control of myeloid cell function is clearly warranted.Our proposal aims to address this problem directly, by investigating a newly identified family of myeloid receptors. This family is orthologous to a previously identified human receptor, CMRF-35A, and we have thus named them CMRF-35 like molecules (CLM). CLMs are expressed predominantly by myeloid cells.Our initial studies have been focused on one receptor, CLM-1 and suggest that CLM-1 can block osteoclastogenesis at an intermediate stage of differentiation. Because of the evident and implied importance of this receptor family in the regulation of myeloid cells, I am interested in pursuing studies of their function.The studies will be focussed in the following areas:- Complete definition of the CLM receptor family. Initial studies will focus on a more thorough definition of the receptor family in terms of cell and tissue expression.- Signal transduction studies. We will first attempt to define proteins associating with select CL M receptors, and will use cytoplasmic domain mutants to further delineate signalling pathways engaged by these receptors.- Ligand identification. A key to determining receptor function is identification of the receptor ligands. This is a particularly challenging task, and to increase chance of success we will use a number of novel library-based approaches.- Functional studies. Even prior to ligand identification, we will use monoclonal antibodies to initiate functional studies of the CLMs. These will be influenced by cell expression, but they are likely to include typical myeloid cell assays.
Original text from CORDIS.
Participants
- UNIVERSITY OF OSLO · OSLOCoordinatorNorway
Links
Data: CORDIS, © European Union