Project: Immunoregulatory functions of the MARCH family of ubiquitin ligases
Villadangos Group
Cell viability and function always requires maintenance of the correct protein composition and distribution within the cell. This proteostasis is regulated by mechanisms that control protein synthesis, localisation, and degradation. Cells can also respond to external signals to alter proteostasis, allowing them to adapt to changes in their environment. In cells of the immune system, expression of many important receptors is regulated by addition of the protein Ubiquitin by the MARCH family of ligases. MARCH ubiquitination plays major roles in immunity against pathogens and cancer. The MARCHs are also involved in inactivation of infecting viruses. However, we know very little about how the MARCHs carry out these important functions. This project will employ biochemical techniques, microscopy, proteomics, and CRISPR-Cas9 technology to characterise the function of the MARCH family; identify novel MARCH substrates; and characterise the machinery involved in ubiquitination by the MARCHs.
Further reading:
H Liu … JA Villadangos* and JD Mintern*. 2016. Ubiquitin ligase MARCH 8 cooperates with CD83 to control surface MHC II expression in thymic epithelium and CD4 T cell selection. J Exp Med 213: 1695-1703. PMID: 27503069.
A Liu, JD Mintern* and JA Villadangos*. 2019. MARCH ligases in immunity. Curr Opin Immunol 58:38-43. PMID: 31063934.
P Schriek,… JD Mintern* and JA Villadangos*. 2021. Physiological substrates and ontogeny-specific expression of the ubiquitin ligases MARCH1 and MARCH8 in mice. Curr Res Immunol. 2: 218-228. PMID: 35492398.
H Liu, … JA Villadangos* and JD Mintern*. 2022. Ubiquitin-1 like protein 3 (UBL3) is required for MARCH ubiquitination of Major Histocompatibility Complex class II and CD86. Nat Commun. 11: 1934. PMID: 35411049.
Contact project supervisor for further
information and application enquiries
Villadangos Group
6 vacancies
The Villadangos group studies the first event that triggers adaptive immune responses: the presentation of pathogen or tumour antigens to T cells by Dendritic Cells, B cells and Macrophages. We are characterizing the development, regulation and impairment of antigen presenting cells by pathogens, inflammatory mediators and tumours. We are also dissecting the biochemical machinery involved in antigen capture, processing, and presentation. We use this knowledge to understand how T cell-dependent immunity is initiated and maintained and apply it to design better vaccines and immunotherapies against infectious agents and cancer.
All our projects are open to Honours/Master of Biomedical Science students and PhD/MPhil graduate researchers
Villadangos Group Current Projects
-
The immune signature of sepsis
PhD/MPhil, Master of Biomedical Science, Honours
-
Regulating macrophage 'eating' for cancer and pathogen control
PhD/MPhil, Master of Biomedical Science, Honours
-
Trogocytosis: a novel communication system between cells of the immune system
PhD/MPhil, Master of Biomedical Science, Honours
-
Improving the formation of protective immunity against human viruses
PhD/MPhil, Master of Biomedical Science, Honours
-
A novel link between metabolism and immune function: O-GlcNAc glycosylation
PhD/MPhil, Master of Biomedical Science, Honours
-
Immunoregulatory functions of the MARCH family of ubiquitin ligases
PhD/MPhil, Master of Biomedical Science, Honours
-
Understanding the causes of immune paralysis and secondary infections in sepsis and trauma patients
PhD/MPhil, Master of Biomedical Science, Honours
-
Harnessing the power of RNA vaccines and therapeutics
PhD/MPhil, Master of Biomedical Science, Honours
-
MR1 – a molecular detection system for bacteria
PhD/MPhil, Master of Biomedical Science, Honours