Rossjohn Laboratory

Understanding immune function and dysfunction.

postdoc
Dr. Gabrielle Watson
Research Fellow

RESEARCH INTERESTS

Our group investigates immune recognition by natural killer cell receptors and mechanisms of viral immune escape.

  1. Understanding immune avoidance by cytomegaloviruses

45-100% of the adult population is infected with the b-herpesvirus human cytomegalovirus (HCMV) and although the infection can seem relatively benign in healthy individuals, HCMV infection is a major cause of death for the immune compromised, such as organ transplant patients.  Cytomegaloviruses have evolved an arsenal of proteins or ‘immune evasins’ that shield the immune system from detecting viral presence, thus leading to lifelong infections. Our group investigates the mechanism of action of these immune evasins at the molecular level with the aim to uncover new targets for the development of novel antiviral therapies.

  1. Investigating ligand recognition by natural killer cell receptors

Natural killer (NK) cells use cell surface activating and inhibitory receptors to sense virally infected, transformed and stressed cells. The inhibitory receptors act as brakes for the immune system, to ensure surrounding tissue is protected while achieving maximal effector responses. Cancerous cells frequently overexpress ligands for the inhibitory receptors to evade immune detection and destruction, and as such, novel immunotherapies blocking the inhibitory receptors are having impressive effects for cancer patients, particularly patients with metastatic melanoma. However, some patients still respond poorly to these treatments.  Understanding the biology of other inhibitory receptors is critical for the development of novel anti-cancer agents, as well as broaden our understanding of innate immune responses. Our group investigates these cell surface receptors at the molecular level to define the basis for ligand recognition and identify unique features that could be exploited for therapeutic design.

Our group are experts in a range of biochemical techniques: molecular biology, protein expression (bacterial, mammalian, insect), protein purification strategies, biophysical techniques (surface plasmon resonance, analytical ultracentrifugation, isothermal calorimetry) and structural determination methods (X-ray crystallography).

RESEARCH PROJECTS

  1. Structural investigation of immune evasins from cytomegaloviruses
    • Investigating immune evasins that block antibody dependent cellular cytoxicity
    • Characterising immune evasins that restrict antigen presentation to T cell and NK cells
  1. Defining ligand recognition by natural killer cell receptors
  • Characterising the CD96 inhibitory receptor and the impact of alternative splicing on ligand recognition
  • Investigating ligand recognition by the natural cytoxicity receptor, NKp44