Developing selective PDE4B-targeting PROTACs to modulate inflammation and improve animal health
Supervisors
Dr Neil Dawson, Division of Biomedical and Life Sciences, Lancaster University
Dr María Paz Muñoz-Herranz, Department of Chemistry, Lancaster University
Andrew Fielding, Division of Biomedical and Life Sciences, Lancaster University
CASE PARTNER - Astra Zeneca
Summary
Animal disease can cause severe inflammation that damages tissues, reduces welfare and increases morbidity. This PhD will investigate PDE4B, an enzyme that regulates cellular cAMP signalling and inflammatory responses, as a new host-directed target for controlling pathological inflammation, to enhance animal health and welfare.
The student will develop selective PROTAC molecules that recruit PDE4B to the cell’s protein degradation machinery, aiming to remove PDE4B rather than simply inhibit its activity. The project will synthesise and optimise candidate degraders, and test their selectivity and impact on inflammatory cellular and signalling mechanisms in cell systems. Lead compounds will then be evaluated in an animal model of inflammation, with outcomes focused on pathological inflammation, tissue damage/recovery and preservation of host defense mechanisms.