About Professor Nicholas Manolios

To develop a better understanding of auto-immune disorders and to provide alternative treatments to these conditions.

Professor Nicholas Manolios research interests are: (i) Structure and assembly of the T-cell antigen receptor, in particular, its role in the predisposition and causation of auto-immune and inflammatory rheumatic disorders, and (ii)Structure-function relationships of T cell assembly and T-cell activation, and how synthetic peptides may be used as therapeutic agents to suppress inflammation.

Professor Manolios is Director of Rheumatology Westmead Hospital and Professor in Medicine, University of Sydney. He is involved in clinical service to Westmead Hospital, administration, teaching and research within the department. Professor Manolios is one of only a few leading academic rheumatologists in Australia who has been able to combine basic scientific research with clinical practice and administration. He founded and established research and academic rheumatology at Westmead Hospital. The unit has had a number of PhD, Master of Medicine and Honours students and a large number of elective overseas students together with volunteer workers. The unit has attracted post-docs from various countries including, China, Sri-Lanka, India, Jordan and Japan who have made significant and vital contributions to research. The unit has a vocational trainee programme, runs a number of clinical trials and attracts enthusiastic and dedicated doctors from overseas for clinical training. The most significant research contribution has been to define the structure-function relationships between individual TCR chains and the assembly of the TCR. In 1990 a seminal observation was published by the applicant that confirmed the importance of transmembrane charges in T-cell antigen receptor assembly (Manolios et al (1990) Science, 249:274-277,) and identified the transmembrane sequence involved in subunit receptor interaction. This paper exemplified how transmembrane regions serve as critical sites for protein-protein/lipid interactions. It also allowed new means to inhibit receptor function. Subsequently the stoichiometry and subunit interactions were defined and published (Manolios et al (1991) EMBO J, 10:1643-1651). Following from these results another important paper was published (Manolios et al (1997) Nature Medicine, 3: 84-87) which described the ability to design and engineer new therapeutic agents based on transmembrane charge interactions and gave “proof of principle” that such an approach was feasible. These observations led us to suggest that targeting intramembrane interactions of TCR with designed molecules may allow for specific regulation of receptor function. Transmembrane peptides today are a very active area of research with great scientific and commercial potential.

Selected publications

For a comprehensive list of Professor Manolios's publicatons, please visit his Sydney Medical School profile page.