Next generation cancer therapeutics targeted with high affinity monomeric glycopeptides
Project ID: 2531bd1703
(You will need this ID for your application)
Research Theme: Healthcare Technologies
Research Area(s): Biological Chemistry & Chemical Biology
UCL Lead department: School of Pharmacy
Lead Supervisor: Chris Morris
Project Summary:
LYsosome-TArgeting Chimeras (LYTACs) are a new concept in cancer medicine. Rather than inhibiting the activity of cancer-causing proteins, they direct them for destruction within the cell’s destructive lysosome compartment. Targeting the proteins to the lysosome has been achieved using ligands for mannose-6-phosphate receptor and the asialoglycoprotein receptor (ASGPR). To date, LYTACs have used large, complex ligands such as multivalent sugars or glycopolymers. These ligands are complex and costly to manufacture at scale.
Why this research is important: To overcome the challenges of complex targeting ligands, this PhD project will use a new class of monovalent small glycopeptides less than 2 kDa, which bind ASGPR with high affinity. Better ligands will lead to more effective drug delivery, easier downstream manufacture and better outcomes for patients with cancer.
Who you will be working with: You will join the Morris and Chudasama groups in the Schools of Pharmacy and chemistry. You will join a multidisciplinary group of post-doctoral and doctoral researchers working on a range of ambitious projects across several diseases including cancer, infection and neurodegeneration.
What you will be doing: You will develop a rounded skillset through training in a range of synthetic, analytical and biological techniques. These will include glycopeptide synthesis and characterisation, antibody-drug and antibody-glycopeptide conjugation reactions, cell culture and drug activity studies. Examples include oxime and Click conjugations, SDS-PAGE, LC-MS/MS, flow cytometry, confocal microscopy.
Who we are looking for: You will have a strong background in chemical/biochemical sciences and a strong ambition to contribute to novel drug development. You will be open-minded, a good team-player and willing to learn new techniques.