"By developing biosensor technology we aim to create simple, cheap tests that will transform infection diagnosis and monitoring in dementia and beyond." Paul Freemont
UK DRI Group Leader
An internationally renowned researcher, Prof Paul Freemont uses structural and synthetic biology tools to investigate molecular mechanisms and detection of disease. Chair in Protein Crystallography and Head of the Section of Structural & Synthetic Biology in the Department of Infectious Disease at Imperial College London, he has authored over 240 scientific papers. In 2009 he co-founded the Imperial College Centre for Synthetic Biology, and in 2013 the National UK Innovation and Knowledge Centre for Synthetic Biology (SynbiCITE). Paul joins the UK DRI Care Research & Technology Centre at Imperial to lead a group researching next-generation biological sensing devices for people with dementia.
1. At a glance
Developing cutting-edge biosensors to detect infection and improve the lives of those living with dementia
Prof Paul Freemont is developing state-of-the-art biological sensing devices encoded entirely by synthetic DNA, which are set to transform the care of people with dementia. He is aiming to create simple, cheap tests that can detect infections and offer exciting new opportunities to improve the early diagnosis and monitoring of a person’s disease.
Recent advances in technology are providing exciting new opportunities to create sophisticated paper-based tests that can accurately detect subtle biological changes in the body. The team are now applying the power of these new biosensors to improve dementia care. They will initially focus on detecting urinary tract infections, which are the most common cause of infection in the elderly. Their aim is to develop a reliable diagnostic test and integrate this into a care pathway that includes communication with GPs who can initiate rapid treatment, avoiding the need for hospital care.
The researchers are also developing ways to use biosensors to detect subtle changes to molecules in blood. Their goal is to create a system that can reliably diagnose dementia early when interventions may be most effective – or to monitor the progression of disease. Developing low-cost simple tests could lead to the implementation of new screening programmes in the future.
2. Scientific goals
This UK DRI programme, led by Prof Paul Freemont, will design and develop next-generation biological-sensing devices encoded entirely by synthetic DNA for dementia-related diagnostic testing. Recently, paper-based biosensors have been developed. Such devices act like ‘litmus’ tests, providing universal usability at low cost. In parallel, new developments in the gene-editing CRISPR/Cas9 system now make it possible to discriminate single-base-pair changes in DNA. Together, both approaches offer the transformative potential for low-cost point-of-care diagnostics.
The researchers will develop new point-of-care diagnostics to allow co-morbid infections to be identified rapidly. The rapid diagnosis and treatment of conditions have the potential to dramatically change the care pathway for people with dementia. Infections are common but often missed. Early diagnosis and treatment would reduce hospital admissions and limit the effects on neurodegeneration and cognitive function. Building on their previous work, the team will now develop the technology for use in dementia, initially in the context of urinary tract infections (UTIs) – the most common cause of infection in the elderly and a major cause of morbidity in dementia. They plan to integrate the biosensor tests into the ‘Healthy Home system’ and produce care pathways that include communication with GPs who would initiate rapid treatment. This technology will also provide new strategies for clinical discovery science. For example, by enabling long-term, accurate monitoring of infections, it will facilitate the detailed investigation of the relationship between infections, brain function and changes in cognition.
In parallel, the researchers will establish a synthetic biology biosensor platform for point-of-care biomarker testing. Current approaches to diagnosis and monitoring of disease progression are limited and new approaches are needed. Synthetic biology allows novel approaches for testing markers of inflammation and neurodegeneration including plasma microRNA and protein profiling. This allows the investigation of dynamic changes of neurodegeneration and inflammation, as well as their relation to general health and behaviour. Proof-of-concept studies will be conducted to test the technology. MicroRNAs are a promising target but current detection approaches all require sophisticated infrastructure and are not suitable for point-of-care testing. To address this, the team will evaluate novel systems to detect and quantitate relative levels of circulating microRNAs from blood samples. Their aim is to combine the assessment of a range of circulating microRNAs to inform the assessment of disease progression and treatment response. They will implement the tests on paper to provide a low-cost, reliable method for quantifying (direct and relative) microRNA levels at large scale, allowing repeated testing of large populations.
Main objectives and research goals:
1. To develop specific point-of-care infection diagnosis using new synthetic biology technology.
2. To establish a synthetic biology biomarker detection platform for the assessment of novel approaches to point-of-care neurodegenerative testing.
3. Team members
Dr Loren Cameron (Postdoctoral Research Associate)
Dr Michael Crone (Research Assistant)
Dr Kirsten Jensen (Project Manager)
Within UK DRI:
- Prof David Sharp, UK DRI Care Research & Technology at Imperial
- Prof Payam Barnaghi, UK DRI Care Research & Technology at Imperial
Beyond UK DRI:
- Prof Tom Ellis, Imperial College London
- Prof Graeme Cooke, Imperial College London
- Dr Karen Polizzi, Imperial College London
- Prof Richard Murray, Caltech
- Prof Jim Ajioka, University of Cambridge
Synthetic biology, biosensors, co-morbid infections, point-of-care diagnostics, microRNA
Next-generation biological sensing devices, CRISPR/Cas9, synthetic biology
7. Key publications
Kylilis N, Riangrungroj P, Lai H-E, Salema V, Fernández LÁ, Stan G-B, Freemont PS*, Polizzi K*, (2019), Whole-cell biosensor with tuneable limit of detection enables low-cost agglutination assays for medical diagnostic applications., ACS Sens.
Moore SJ, MacDonald JT, Wienecke S, Ishwarbhai A, Tsipa A, Aw R, Kylilis N, Bell DJ, McClymont DW, Jensen K, Polizzi KM, Biedendieck R, Freemont PS (2018), Rapid acquisition and model-based analysis of cell-free transcription-translation reactions from nonmodel bacteria., Proc Natl Acad Sci USA April 17.
Rajakumar PD, Gower G, Suckling L, Kitney R, McClymont D, Freemont Pclose, 2018, Rapid prototyping platform for Saccharomyces cerevisiae using computer-aided genetic design enabled by parallel software and workcell platform development, Slas Technology, vol 24 291-297.
Wen KY, Cameron L, Chappell J, Jensen K, Bell DJ, Kelwick R, Kopniczky M, Davies JC, Filloux A, Freemont PS, 2017, A Cell-Free Biosensor for Detecting Quorum Sensing Molecules in P. aeruginosa-Infected Respiratory Samples., ACS Synthetic Biology, Vol: 6, Pages: 2293-2301.
Webb, A. J., Kelwick, R., Doenhoff, M. J., Kylilis, N., MacDonald, J. T., McKeown, C., Baldwin, G., Ellis, T., Jensen, K., Freemont P. S. (2016). A protease-based biosensor for the detection of schistosome cercariae.Sci Rep, 6, 24725. doi:10.1038/srep24725.