Engineering Feedback Control Loops into CAR-T Therapeutics

This PhD project at University College London focuses on engineering feedback control loops into CAR-T cell therapeutics to address key limitations in current cancer immunotherapy. CAR-T therapy has transformed treatment for certain blood cancers, but challenges such as severe cytokine release syndrome and manufacturing variability persist. The research aims to develop 'self-regulating' CAR-T cells that can sense their own population density and automatically adjust their activity, thereby reducing the risk of dangerous overactivation while maintaining therapeutic effectiveness. This innovation has the potential to significantly improve the safety and reliability of CAR-T therapies. The successful candidate will join a multidisciplinary team in the Department of Biochemical Engineering and Department of Mathematics, working under the guidance of Dr Darren Nesbeth (engineering biology and cell therapy bioprocessing) and Professor Alexey Zaikin (mathematical modeling and systems biology). The project will involve designing, constructing, and characterizing artificial genetic circuits in mammalian cells, with initial proof-of-concept experiments using fluorescent reporters. The student will then engineer immortalized T cells with circuits that regulate cytotoxic function in response to cell crowding. Training will cover molecular cloning, DNA assembly, mammalian cell culture, lentiviral transduction, flow cytometry, genetic circuit design, data analysis, and integration of experimental results with mathematical modeling. The studentship is fully funded for four years, covering tuition fees (with additional support for international students), a tax-free stipend at an enhanced rate, and a Research Training Support Grant for additional training and project costs. Applicants should have a strong background in life sciences, bioengineering, biotechnology, or related fields. While prior experience in molecular biology or mammalian cell culture is beneficial, it is not required. The team values curiosity, creativity, problem-solving skills, and enthusiasm for interdisciplinary collaboration. The application deadline is January 5, 2026, and applications must be submitted via the official UCL EPSRC Doctoral Training portal. For further information or technical queries, candidates can contact the DTP Manager at [email protected].