Professor EmeritusNicholas Manolios

Project Opportunities

Title: Phosphoproteomics in early T-cell signalling

Summary of opportunity:

Using phospho-proteomics to understand T-cell signalling/signal transduction.

Opportunity synopsis:

This project focuses on the structure-function relationships underlying T-cell antigen receptor (TCR) activation following antigen recognition. The exact molecular arrangement of the TCR/CD3 complex and the spatial positioning of these contact sites leading to signalling have not been fully elucidated. Recent functional insights gained from our studies on TCR signalling have enabled us to extend the current signaling paradigm and propose a novel and alternate pathway involved with TCR signalling. We will use proteomic techniques to identify which proteins are involved in early stage T-cell signalling and prove or disprove the alternate pathway hypothesis. The second phase of the project using in silico computational analysis would be to design and test peptides able to inhibit either of the pathways identified. More specifically: 
1. Apply phospho-proteomic techniques to define proteins in TCR signal transduction following ANTIGEN stimulation.
2. Use both target and ligand-based in silico computational techniques to investigate and establish the nature of contributing extra-cellular binding interactions specific to TCR-b and CD3-e and other peptide inhibitors of TCR signalling pathways.

Project Opportunities

Title: THE USE OF MARIJUANA AND/OR ENDOCANNABINOID OILS FOR THE TREATMENT OF OSTEOARTHRITIS (OA)

Summary of opportunity:

Pre-clinical studies for the effects of CBD and analogues for the treatment of osteoarthritis

Opportunity synopsis:

The aim of this study is to evaluate topical applications of cannabidiol (CBD), an active constituent of marijuana, or endocannabinoid analogues [linoleoylethanolamide (LEA), oleoyl ethanolamide (OEA), and palmitoylethanolamide (PEA)] applied as topical patches, to reduce joint pain in OA patients. This study will provide valuable information, into the much needed, pharmacokinetics of endocannabinoids and their effectiveness/utility in pain relief. By using CBD or endocannabinoid analogues that stimulate only the cannabinoid 2 receptor (CB2) it is hypothesised that the previously published side effects of drowsiness and confusion (CB1 effects) will not be observed and the patients will benefit from pain relief.
This study is novel in the use of compounds not previously tested (OEA, LEA, PEA) in OA; the effectiveness of transdermal administration of these drugs in humans; and the development of a unique patch delivery system. The application of these finding will have a direct impact on individuals with pain providing analgesia and anti-inflammatory effects without the hallucinations or drowsiness often noted with marijuana; create a new delivery system; provide valuable information on CBD, OEA and PEA in patients with OA that can form a platform for future studies and adaptation into clinical practice.

Project Opportunities

Title: Towards a cure for Type I diabetes mellitus

Summary of opportunity:

Transfect a lentivirus construct expressing an immunosuppressive peptide in islet cells for the treatment of diabetes type I

Opportunity synopsis:

Type 1 diabetes is a T-cell mediated disease. Local production of an immunosuppressive peptide by means of gene therapy of islet cells would have a specific local T-cell effect while circumventing generalized immunosuppression. In this project islets will be isolated and transfected ex-vivo with a lentiviral construct engineered to secrete an immunosuppressive peptide, called core peptide (CP). The transfected islets will then be transplanted into HLA mismatched mice. It is hypothesized that the local release of immunosuppressive peptide will prevent rejection, enhance islet survival and control blood sugar levels.