SFI UREKA Site in Molecular Recognition
Translating Design into Application

Molecular Design

Project 4:        Using Rational Design and Directed Evolution to Develop Novel Apoptosis-Inducing Molecules

Supervisor:     Prof. Afshin Samali, Department of Biochemistry

Project Summary:  A major aim of anti-tumour therapies is to inhibit proliferation and induce death of tumour cells without affecting normal cells. In this regard, members of the Tumor necrosis Family (TNF) ligand/receptor family are of interest since they regulate both apoptosis (programmed cell death) and cell proliferation (cell growth). One TNF family member, TRAIL, is of particular interest since it selectively induces death of tumour cells without affecting normal cells. Currently, TRAIL and TRAIL-specific antibodies are being investigated as anti-cancer agents. However, a major drawback to TRAIL’s efficacy is that it binds to multiple receptors, not all of which transduce an apoptotic signal.

Current research of the laboratory investigates and characterises TRAIL variants pre-clinically in solid tumour models and define new treatment protocols in combination with already proven treatments. Using biochemical and structural characterisation we aim to identify new targets for molecular cancer therapy while computational design and molecular evolution techniques are used to develop novel receptor-selective apoptosis-inducing agonists. Our laboratory together with our collaborators work on developing novel molecules that target critical apoptotic signalling pathways important in the formation and survival of various solid tumours.

The student will work daily with Dr. Eva Szegezdi, a Senior Research in Dr. Samali’s laboratory, and will be trained by her on a diverse range of techniques relevant to the project.  Specifically the student will gain experience in both computer-based rational design and molecular evolution techniques that involve the execution of computer-based design programmes and molecular biology techniques in the laboratory. 

• Disclaimer
• Privacy
• Copyright
• Accessibility