Investigating the role of the chemokine receptor ACKR3 in immune signalling and disease.

This project is suitable for an Honours, Masters or PhD student.

BACKGROUND

Chemokines are a class of signalling molecules that are important for maintaining homeostasis and the inflammatory responses of cells. Chemokine receptors respond to these molecules by signalling to cells to proliferate or move. In addition to these classical chemokine receptors, there are also atypical chemokine receptors, which are poorly understood.

The atypical chemokine receptor ACKR3 (also named CXCR7) has been implicated in cancer survival and metastasis and is also protective against fibrosis. ACKR3 can bind to the chemokines CXCL11 and CXCL12, as well as other non-chemokine signalling molecules. ACKR3 has been proposed as a key receptor to target developing therapeutics for cancer and fibrosis, however there is a significant gap in the current knowledge about the role of this receptor in normal physiology and immune signalling.

Our research group has begun characterising the role of ACKR3 and the cell populations that express it. This project will further explore how ACKR3 regulates immune cell function at steady-state, following immunization, and in diseases like lupus and cancer.

AIMS

The aims of this project are to:

• Determining the cell types that express ACKR3 and investigate the role that ACKR3 plays.
• Analyse mice that lack ACKR3 on specific cell types of interest.
• Define the role of ACKR3 in immunity, such as the T cell-dependant and T cell-independent immune responses.
• Investigate the role of ACKR3 on self-reactive B cells.

Through these studies, the student will gain significant expertise in mouse models of disease, cell culture, flow cytometry, immunohistochemistry and other laboratory techniques.

PROJECT POTENTIAL

To pioneer knowledge in a neglected area of immunology, validate these findings with human immune cells and publish a high impact, world-first discovery. This project has the potential to uncover aspects of autoimmunity never contemplated before.