Exploring the therapeutic potential of chimeric proteins
Lead Research Organisation:
University of Cambridge
Department Name: Biochemistry
Abstract
This projects aims to design and evolve proteases with therapeutic potential following a new conceptual approach, in which separate binding and catalytic domains are covalenty combined in chimeric 'captivases'. This will overcome the difficulty of engineering both binding and catalytic functions in one active site, instead relying on modular design principles. Starting points for this effort are one one hand existing antibodies (to provide binding) and on the other the catalytic potential of proteases with promiscuous activities (see 'Combinatorial Screening Identifies Novel Promiscuous Matrix Metalloproteinase Activities That Lead to Inhibition of the Therapeutic Target IL-13; C. Urbach, et al. & F Hollfelder, and L Jermutus; Chemistry & Biology (2015), 22(11):1442-52). Later such constructs will be evolved (see ChemBioChem.doi: 10.1002/cbic.201500295 - and using ultrahigh-throughput screening in microfluidic droplets - see Nature Communications 2015, 6:10008- DOI: 10.1038/ncomms10008), mechanistically characterised and improved and then tested on medically relevant targets (with collaborators at MedImmune).
Organisations
People |
ORCID iD |
Florian Hollfelder (Primary Supervisor) | |
Katrin Fischer (Student) |
Studentship Projects
Project Reference | Relationship | Related To | Start | End | Student Name |
---|---|---|---|---|---|
MR/N013433/1 | 30/09/2016 | 29/04/2026 | |||
1947736 | Studentship | MR/N013433/1 | 30/09/2017 | 29/09/2021 | Katrin Fischer |