Overall purpose:
The postdoctoral researcher will join a multi-disciplinary team working on a multi-lab team science initiative aimed at understanding and modulating cytosolic nucleic acid sensing pathways involved in chronic inflammation and ageing ("inflammageing"). The successful candidate will integrate advanced single-molecule biophysics, protein biochemistry, chromatin biology, and translational pharmacology to deliver key mechanistic and therapeutic insights.
The postholder will employ optical tweezers combined with fluorescence imaging to directly visualise nucleic acid sensor interactions with DNA and RNA substrates under applied force. These real-time, quantitative analyses will reveal how sensors such as cGAS, AIM2, RIG-I, MDA5, and TLR9 are modulated by nucleic acid structure, chromatin context, and post-translational modifications.
Alongside this, the postdoc will take a leading role in the design and development of biochemical assays for high-throughput drug screening. In collaboration with the LMS/Imperial Drug Discovery Hub (DDHub), they will execute compound screens to identify inhibitors, activators, and degraders of key nucleic acid sensors, followed by mechanistic validation using biophysical and biochemical platforms. This position sits at the interface of fundamental research and therapeutic discovery.
Main duties / key responsibilities:
* Design and execute molecular cloning, protein expression, and purification strategies for recombinant nucleic acid sensors
* Plan and conduct optical tweezer-based single-molecule assays to characterise DNA/RNA sensor dynamics
* Develop and optimise in vitro assays (e.g. fluorescence-based, enzymatic, binding) for use in compound screening
* Work with DDHub to perform high-throughput screening for small-molecule modulators
* Analyse screening data and characterise compound hits using biochemical, biophysical, and structural techniques
* Collaborate with other scientists to validate compounds in cellular models of senescence and ageing
* Provide training and support to junior lab members, including PhD students.
* Participate in regular lab meetings, journal clubs, and institute seminars.
* Write scientific papers and present findings at national and international conferences.
* Take an active part in the academic activities of the LMS
* Form good working relationships with other members of LMS groups as well as internal and external collaborators