Emerging infections and antibiotic resistance rank among the gravest threats to human health alongside global warming and terrorism. My research aims to transform the early diagnosis, treatment and tracking of deadly outbreaks - including new strains of influenza, antimicrobial resistance and HIV – by exploiting advances in nanotechnology, telecommunications and big data.
Recent research highlights span from unravelling the nanomechanical workings of antibiotics against MRSA (Nature Nanotechnology 2014), to creating mobile phone connected diagnostics for HIV (NIHR i4i award with OJ-Bio) and a major new £11M EPSRC IRC in global early warning sensing systems, linking self-reported symptoms on social media and search engines with mobile phone-connected disease diagnostics:
- Superbugs and superdrugs: Alexander Flemings’ serendipitous discovery of penicillin heralded a golden era of antibiotic drug discovery but in recent years the drug pipeline has dried to a trickle and new antibiotics are urgently needed. My team is using cantilever ‘diving board’ sensors to unravel the remarkable nanomechanical molecular workings of vancomycin, one of the few effective treatments for MRSA on drug susceptible and drug resistant phenotypes. Our percolation framework provides new insight into how drug binding mechanically weakens cells leading to death by lysis (Nature Nanotechnology 2008). More recently we have developed analytical models to disentangle the interplay between antibiotic levels in serum and their efficacy on the surface of bacteria for ultra-sensitive therapeutic monitoring applications. Our findings may also aid drug discovery of new antibiotics against drug resistance. (Nature Nanotechnology 2014). http://www.nature.com/nnano/journal/v9/n3/full/nnano.2014.33.html; http://www.nature.com/nnano/journal/v8/n7/full/nnano.2013.127.html
- Mobile phone connected diagnostics for HIV
Globally HIV currently infects 33 million men, women and children but even in the UK, one in four people are unaware of their infection. Working with industry partners OJ-Bio and clinicians at UCL/UCLH BRC and UCL Partners, we are creating a new generation of mobile phone-connected diagnostic devices to help widen access to testing in community settings and developing countries. Our approach combines innovative surface acoustic wave biosensors developed by OJ-Bio with UCL’s llama antibodies coatings - small temperature stable antibodies with a high affinity for HIV.
Collaborators: Robin Weiss, Deenan Pillay, (UCL); Vince Emery (Surrey) and Dale Athey, Hiromi Yatsuda (OJ-Bio www.oj-bio.com)
Acknowledgement: The II-LA-1111-20004 project is funded by the National Institute for Health Research’s Invention for Innovation Programme.
- Hunting Pathogens (EPSRC IRC i-sense)
Emerging infections arise can spread rapidly with the ability to cause pandemics e.g H1N1 Spanish Flu and SARS. Early detection of outbreaks plays a vital role in helping patients gain quicker access to treatment and protecting the wider public from the risk of deadly infection. However, today, limited diagnostic technologies in community settings mean that infections are often picked up at a late stage, leading to ongoing transmission within communities and delays in public health efforts to respond to emerging threats e.g. pandemic influenza.
We have recently been awarded a major new £11M EPSRC interdisciplinary research collaboration (i-sense) to build early-warning sensing systems to identify outbreaks – including new strains of influenza, antibiotic resistance and HIV - much earlier than ever before by linking web information sources to mobile phone connected tests. We are investigating if self-reported symptoms of infection on social media (Twitter) and search engines (Google and Bing) can help to accurately identify outbreaks across populations, in real-time with geographically linked information, even before people attend clinics. Since many diseases share common symptoms we are linking these big data sources to mobile phone-connected diagnostic tests – including ‘barcodes’ of host and pathogen biomarkers which can be read using smart phone cameras via an ‘app’. The ability to transmit results and location immediately into clinical and public health systems will help patients gain more rapid follow up care and protect populations from the spread of deadly infections.
The IRC is a 5 year, EPSRC funded collaboration between UCL, Imperial, LSHTM, Newcastle, Surrey and Public Health England with clinical and industry partners- UCL: Deenan Pillay (Wellcome Trust Africa Centre), Anne Johnson, Ingemar Cox, Andreas Demosthenous, Quentin Pankhurst, Eleni Nastouli (UCL Partners), Andrew Hayward, Dorothy Duffy; Imperial: Molly Stevens; LSHTM: Rosanna Peeling; Newcastle University: Calum McNeil, Neil Keegan, Colin Harwood, Anil Wipat and Phil Manning; Surrey University: Vince Emery; Clinical Partners: UCL/UCLH BRC, UCL Partners, Newcastle Upon Tyne Hospitals NHS Trusts, Newcastle BRC, the International Diagnostics Centre (LSHTM), Wellcome Trust Africa Centre for Health and Population Studies; Public Health England: Mike Catchpole and Richard Pebody; Industry: OJ-Bio, Microsoft, O2 Health, Mologic (Alere), Zurich Instruments, X-FAB, Cambridge Life Sciences, Avacta and Cepheid.
*** Join our ‘New Frontiers in Digital Technologies for Influenza: Big Data and Mobile Phone Connected Diagnostics’ workshop on 26th June 2014 in London. The meeting is being jointly organized with the UK Infectious Diseases Research Network with high profile speakers from PHE, Google, Harvard, Telefonica, OJ-Bio, UCL, LSHTM and Imperial http://www.ucl.ac.uk/infection-sense/upcomingevents
*** Our £500K Exploratory Funding call is now open for new research early warning sensing systems for influenza. The closing date is 1st July. For more information please see the i-sense website: http://www.ucl.ac.uk/infection-sense
Selected Publications
[1] ‘Surface stress sensors for rapid and ultrasensitive detection of active free drugs in human serum’ Ndieyira, J. W., Kappeler, N., Logan, S., Cooper, M. A., Abell, C., McKendry, R. A.* & Aeppli, G. Nature Nanotech. 9, 225 (2014). Featured in Nature Nanotechnology News and Views. Top 10 Nature Nanotechnology download in March 2014.
[2] ‘Good Vibrations for Bad Bacteria’ McKendry R.A.* & Kappeler, N. Nature Nanotech. 8, 483 (2013).
[3] ‘Differential stress induced by thiol adsorption on facetted nanocrystals’ Watari M, McKendry, RA; Vögtli, M; Aeppli, G., Soh YA; Shi, X; Xiong, G; Huang, X; Harder R & Robinson, I Nature Materials 10, 862 (2011).
[4] ‘Nanomechanical detection of antibiotic mucopeptide binding in a model for superbug drug resistance.’ Ndieyira, W.N, Watari, M., Donoso-Barrera, A., Batchelor, M., Zhou, D., Vogtli, M., Bactchelor, M., Cooper, M., Strunz, T., Abell, C.A., Rayment, T., Aeppli, G. & McKendry R.A.* Nature Nano. 3, 691 (2008). Featured in Nature Nanotechnology News and Views.
[5] ‘A polarised population of dynamic microtubules mediates homeostatic length control in animal cells’ Picone R., Ren X., Ivanovitch K. D., Clarke J. D., McKendry R. A.* & Baum B. PLoS Biol. 16, 11 (2010). F1000 ranking - top 2% of published articles in biology and medicine.
[6] ‘Rapid and label-free nanomechanical detection of biomarker transcripts in human RNA’ Zhang, J., Lang, H.P., Huber, F., Bietsch, A., Grange, W., Certa, U., McKendry, R. Guntherodt, H., Hegner, M. & Gerber, C. Nature Nano. 1, 214 (2006).
[7] ‘Chiral discrimination by chemical force microscopy’ McKendry, R., Theoclitou, M-E., Rayment, T. & Abell, C. Nature 391, 566 (1998).
RESEARCH TEAM: My team is highly multidisciplinary and includes chemists, virologists, physicists, engineers and medics. Current PDRAs: Eleanor Gray, Natascha Kappeler, Claudio Parolo, Jenny Brookes; PhD Students: Valerian Turbe, Ben Miller, Candice Keane, Kristina Schlegel; Researchers: Alexander (Sandy) Wright; Support staff: Antonio Ruiz-Sanchez (Senior Laboratory Technician), Tania Saxl (Strategic Operations) and Kailey Nolan (Administration and Communications Manager).
We collaborate with academic, clinical and industry researchers in the UK, South Africa, Switzerland, Denmark, Australia, Japan and the USA.
OPEN POSITIONS: I currently have open positions for talented postdoctoral researchers, a senior technician and PhD studentships. If you are interested to apply please contact me at r.a.mckendry@ucl.ac.uk and Kailey Nolan, (i-sense Administration and Communications Manager) at k.nolan@ucl.ac.uk