View Vacancy -- MRC Postdoctoral Research Scientist LMS 2730

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

Education / Qualifications / Training required (will be assessed from the application):

Essential:

• PhD in Biochemistry, Molecular Biology, or Biophysics
• Experience using Lumicks C-Trap-optical tweezers

Desirable:

• Training in drug discovery or assay development

Previous work experience required (will be assessed from the application and at the interview):

Essential:

• Good written communication skills in English
• Experience in protein expression and purification of recombinant proteins
• Experience in developing and executing quantitative biochemical assays
• Experience in the use of single-molecule techniques (specifically- Lumicks C-Trap-optical tweezers)
• Track record of publishing scientific results in peer-reviewed journals
• Experience with high-throughput screening

Desirable:

•  Background in chromatin biochemistry or post-translational modification studies

Knowledge and experience (will be assessed from the application and at the interview):

Essential:

• Understanding of nucleic acid–protein interactions, particularly as relevant to the design and interpretation of single-molecule biophysical experiments
• Proficiency in data analysis from biochemical or biophysical experiments
• Knowledge of assay development for small-molecule screening

Desirable:

• Familiarity with cGAS-STING and related pathways
• Exposure to structural prediction tools (e.g. AlphaFold)

Personal skills/behaviours/qualities (will be assessed at the interview):

Essential:

• Excellent laboratory skills
• Excellent organisational skills
• Excellent attention to detail
• Excellent creativity
• High-Motivation and perseverance
• The post holder should be prepared to work unsociable hours as work demands from time to time
• Ability and willingness to adapt to changing timetables or work patterns as dictated by changing circumstances
• Ability to work under pressure while maintaining a high degree of accuracy
• Proven ability to prioritise, plan ahead and manage a high volume of work to meet deadlines, both prescribed and self-imposed
• Ability to use own initiative and work independently and as part of a team, as required
• Problem solving abilities
• Proven multitasking abilities
• Ability to work in a collaborative research environment
• Willingness to give and receive help with challenging problems
• Good verbal communication skills in English
• Ability to communicate its science in a clear way
• Good interpersonal skills
• Willingness to share knowledge and transfer skills to other members of the group on a daily basis

Applicants should submit one CV, names and contacts of two scientific references, along with a cover letter stating why you are applying for this role (providing evidence against the requirements of the job as per the job description and person specification). Please quote reference number LMS 2730.

Please note that applications may be reviewed by both LMS and Imperial staff