"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 250 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) and is Director of the London Biofoundry. 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 in the home 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 analysing the molecular microbiology of urinary tract infections and applying machine learning and other computational techniques, in order to predict the onset of UTI in people living with dementia.
2. Scientific goals
Approximately one quarter of hospital beds in the UK are made up of people living with dementia with as much as 20 per cent of those admissions due to potentially preventable acute conditions such as infection. The UKDRI programme led by Prof Paul Freemont aims to reduce the burden of infections on people living with dementia by developing in-home tests to monitor common infections such as urinary tract infections and prevent premature hospitalisation and subsequent cognitive decline. To achieve this our overall aim is to conduct in-depth longitudinal studies on people living with dementia to experimentally determine the molecular microbiological, physiological and behavioural changes associated with infections, focusing initially on UTIs.
Despite molecular and microbiological complexities, common features of infections such as UTIs have been identified which include virulence factors and antibiotic resistance markers. Prof. Freemont’s programme aims to systematically extend these investigations to discover new infection biomarkers and also map the landscape of infection. The goal is to deploy in the home, validated tests for common infections, using new and existing infection biomarkers, such that continuous monitoring can allow timely clinical interventions and prevent premature hospitalisation and cognitive decline. By linking clinical background, molecular features of infection, behaviour/cognition and neurodegenerative markers will determine how infections affect neurodegenerative disease progression. 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 also establish a biobank of clinical strains that will be used to identify genetic changes associated with UTI pathogens and/or antibiotic resistance.They will also monitor changes in presence of different microbes and correlate any changes with the onset of UTI’s. The overall goal is identify new microbial biomarkers that can be linked to UTI’s in people living with dementia so that early detection can prevent hospitalisation.
Main objectives and research goals:
- Determine pathogen genetic biomarkers associated with common infections in people living with dementia and develop point-of-care interventions using synthetic biology bioreporters
- Understand the relationship between infections, neurodegeneration, cognitive impairment and behaviour
- Establish collaborative technology pathways for developing a point-of-care device
3. Team members
Dr Bing Li (Emerging Leader)
Dr Kirsten Jensen (Project Manager)
Dr Raphaella Jackson (Postdoctoral Researcher)
Thomas Adam (Research Assistant)
Martin Tran (Research Assistant)
Xiaotong Guo (Research Postgraduate)
Within UK DRI:
- Prof David Sharp, UK DRI Care Research & Technology at Imperial
- Prof Payam Barnaghi, UK DRI Care Research & Technology at Imperial
- Prof Henrik Zetterberg UK DRI at UCL
- Prof David Klenerman UK DRI at Cambridge
Beyond UK DRI:
- Prof Tom Ellis, Imperial College London
- Prof Thomas Heinis, Imperial College London
- Prof Graeme Cooke, Imperial College London
- Dr Karen Polizzi, Imperial College London
- Prof Richard Murray, Caltech, USA
- Dr Simon Moore, Queen Mary College London
Synthetic biology, biosensors, co-morbid infections, point-of-care diagnostics, urinary tract infections
Next-generation sequencing; design and engineering of diagnostic device; automated liquid handling workflows; bioinformatics and machine learning, nucleic acid amplication
7. Key publications
Webb A, Allan F, Kelwick R, Beshah F, Kinunghi S, Templeton MR, Emery A*, Freemont PS* (2022) Specific Nucleic AcId Ligation for the detection of Schistosomes: SNAILS, PLoS Neglected Tropical Diseases, 16(7):e0010632
Gil Rosa B, Akingbade OE, Guo X, Gonzalez-Macia L, Crone MA, Cameron LP, Freemont PS, Choy K-L, Güder F, Yeatman E, Sharp DJ, Li B (2022), Multiplexed immunosensors for point-of-care diagnostic applications, Biosensors and Bioelectronics, 203, 114050
Vickers CE, Freemont PS, (2022) Pandemic preparedness: synthetic biology and publicly funded biofoundries can rapidly accelerate response time, Nature Comms, 13, 453
Kelwick, RJ., Webb, AJ., Wang, Y., Heliot, A., Allan, F., Emery, AM., Templeton, MR, Freemont, PS. (2021) AL-PHA beads: bioplastic-based protease biosensors for global health applications. Materials Today 47, 25
Crone M, Randell P, Herm Z, Anand A, Missaghian-Cully S, Perelman L, Pantelidis P*, Freemont PS* (2021), Rapid design and implementation of an adaptive pooling workflow for SARS-CoV-2 testing in an NHS diagnostic laboratory: a proof-of-concept study, Wellcome Open Research, 6, 1-13,
Crone, MA., Priestman, M., Ciechonska, M., Jensen, K., Sharp, DJ., Anand, A., Randell, P., Storch, M., Freemont, PS. (2020) A role for Biofoundries in rapid development and validation of automated SARS-CoV-2 clinical diagnostics Nature Communications 11: 1-11