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Details of Grant 

EPSRC Reference: EP/R011443/1
Title: Parallelised live microscopy for high-throughput behavioural phenotyping in malaria research
Principal Investigator: Cicuta, Professor P
Other Investigators:
Campbell, Professor NDF Bowman, Dr R W
Researcher Co-Investigators:
Project Partners:
Department: Physics
Organisation: University of Cambridge
Scheme: Standard Research
Starts: 01 July 2018 Ends: 30 June 2021 Value (£): 592,337
EPSRC Research Topic Classifications:
Med.Instrument.Device& Equip. Medical science & disease
EPSRC Industrial Sector Classifications:
Related Grants:
Panel History:
Panel DatePanel NameOutcome
30 Jan 2018 HT Investigator-led Panel Meeting - January 2018 Announced
11 Sep 2017 HT Investigator-led Panel Meeting - September 2017 Announced
Summary on Grant Application Form
Many smaller, simpler microscopes can often see more than one large, expensive machine. We propose to innovate a research-quality, fully automated microscope design that can be tailored to a particular experiment and easily replicated to perform many experiments in parallel. With computer vision to control and analyse these experiments, the bottlenecks of equipment and staff time are removed, and it becomes possible to keep pace with new genetic technologies - even for previously time-consuming studies, for example measuring the invasion of red blood cells by plasmodium parasites. We will develop the microscopy and computer vision technologies, demonstrate their efficacy in our malaria lab and those of our collaborators, and release open-source designs that allow others to replicate our progress. The ability to screen hundreds of different mutant strains efficiently will lead to a deeper understanding of many diseases, ultimately creating new drug discovery targets and potentially leading to new vaccines for conditions like malaria.

Gene editing is in the midst of a revolution thanks to CRISPR-Cas9 protocols, and cell phenotyping needs to keep pace. Specifically in malaria, our collaborators are now scaling up knockouts in P. falciparum using CRISPR, and expect to make 200 knockout lines this year, and 1000 in the next five years . While strain generation is scaling so dramatically , phenotyping is not, i.e. we cannot determine the function of these genes - we need robust and cheap scalable phenotyping assays, which involve live cell imaging, and specifically of host/pathogen invasions. It is not conceivable to perform these assays through current methods and technologies. New, much more automated and affordable approaches to imaging have to be developed and deployed. This would then allow us to systematically screen GM lines for several phenotypes, including merozoite number, cytokinesis, egress and invasion. We address here the case of malaria, but point out that very similar challenges and objectives can be identified in many other infectious diseases.
Key Findings
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Organisation Website: http://www.cam.ac.uk