The complex and mysterious mechanisms that drive communication and reactions within human cells could be on the verge of being unravelled, due to a pioneering new technique.
Researchers from the Universities of Leeds, Exeter and Cambridge have harnessed an innovative new method to gain a greater understanding of signalling stations within the cells, called nanodomains.
They believe the new technique could pave the way for a greater understanding behind the causes of potentially life-threatening conditions such as heart disease, as well as potential new treatment pathways.
The nanodomains are known to drive fundamental physiological processes in the body, including the onset of disease.
Scientists have, until now, generally relied on electron-microscopy to study these structures. However the technology has not allowed access to the finer mechanisms of the nanodomains at a molecular level.
Now, the UK research team have refined a new, light based super-resolution microscopy technique that allows high-quality imaging of the signalling stations in the human heart.
“At present, none of the treatments or therapies provided to heart failure patients specifically target the signalling stations – nanodomains – within the cell, which the evidence overwhelmingly suggests are a major cause of heart failure.
“We believe that by visualising these signalling structures at this level of detail using super-resolution microscopy we can help guide investigations into how we can target or repair these molecular machines and thus, in the long term, help patients to overcome heart disease.”
Expertise in the design of synthetic DNA strands was provided by Dr Lorenzo Di Michele from the University of Cambridge.
The ground-breaking new technique allows scientists to pin-point any number of specific types of proteins within the cells, the counting of each species of protein, and observations of the precise patterns in which they are arranged.
Professor Christian Soeller, who led the study and is at the new Living Systems Institute at the University of Exeter, said: “Slightly more than a decade ago nobody thought that we would ever see individual molecules with light, the resolution just seemed insufficient to resolve such fine detail.”
“Since then an astonishing array of new tricks has been devised. In our latest advance, the use of synthetic DNA has been critical – the deep understanding of the chemistry of DNA we have today makes it an enormously versatile tool.”
As a result, the team says that their research provides a “perfect window” to examine the changes that occur in the molecular machinery which are a major cause of heart failure.
They believe the added visual detail that the new imaging provides will guide more decisive investigations into how to target or repair these signalling stations or the molecular machines within them more precisely.
For additional information and to request interviews with Dr Isuru Jayasinghe, please contact Simon Moore in the University of Leeds press office on +44 (0)113 34 34031 or email@example.com.
The work was supported by funding from the Human Frontier Science Program, the Engineering and Physical Sciences Research Council of the UK, Wellcome Trust, and the Royal Society of the UK.
Stephen Muench with Glaxo SmithKline & UCB Celltech, BBSRC Industrial Partnership Award (Apr 2018), £480,225
Steve Clapcote, BBSRC (Apr 2018), £443,072
Helen Miller, Innovate UK (Apr 2018), £999,960
Elisabetta Groppelli, David Rowlands & Stanley Lemon (University of North Carolina), Medical Research Foundation Fellowship (Apr 2018), £293,494
Nikesh Patel, Medical Research Foundation fellowship (Apr 2018), £290,976
Graham Askew with colleagues in Hull and Liverpool, BBSRC (Apr 2018), £150,498
Andrew Macdonald, Neil Ranson & Richard Foster, Kidney Research UK (Apr 2018), £82,821
Jessica Kwok & Ralf Richter, Leverhulme Trust (Apr 2018), £298,273
Julie Aspden, Royal Society (Apr 2018), £20,000
Liz Duncan, Royal Society (Mar 2018), £14,602
Alex O'Neill & Ryan Seipke, BBSRC (Feb 2018), £45,489
Jim Deuchars, Royal Society (Feb 2018), £16,300
Stefan Kepinski & Netta Cohen, Leverhulme Trust (Feb 2018), £320,387
Lisa Collins, BBSRC (Feb 2018), £49,950
Alison Baker, BBSRC (Feb 2018), £30,000
Lars Jeuken, BBSRC (Feb 2018), £30,000
Nikita Gamper, BBSRC (Feb 2018), £30,000
Scott Bowen, Leducq Foundation Grant (Feb 2018), £28,470
Jessica Kwok and Ronaldo Ichiyama, International Spinal Research Trust (Feb 2018), £94,450
Alex O'Neill, Oxford Drug Design (Jan 2018), £86,098
Dave Lewis and Colleagues in South Africa, HEFCE Global Challenge Research (Jan 2018), £48,000
Sarah Calaghan, Ed White, John Colyer, Isuru Jayasinghe, BHF (Jan 2018), £128,308
Christine Foyer and Alison Baker, HEFCE GCRF Grant (Jan 2018), £71,158
Alison Baker, Yun Yung Gong and Lindsay Stringer and ICRISAT India, HEFCE GCRF Grant (Jan 2018), £27,000
Graham Askew, Simon Walker, BBSRC (Jan 2018), £699,781
Jennifer Tomlinson, Royal Society (Jan 2018), £512,801
Alison Dunn, NERC (Dec 2017), £18,000
Jennifer Tomlinson, Royal Society-Research Fellows Enhancement Award (Dec 2017), £94,681
Helen Miller, AB AGri Grant (Dec 2017), £73,600
Simon Walker, Royal Society Enhancement Award (Dec 2017), £10,000
Carrie Ferguson, Bryan Taylor, Harry Rossiter, The Physiological Society (Dec 2017), £7,392
Ralf Richter, Royal Society (Dec 2017), £6,000
Christine Foyer, British Council Newton Fund (Dec 2017), £49,840
Adrian Whitehouse and colleagues in School of Chemistry and University of Liverpool, MRC (Nov 2017), £622,319
Michelle Peckham, Neil Ransom, MRC (Nov 2017), £495,159
Dave Lewis, British Council India (Nov 2017), £22,540
Elton Zeqiraj, Royal Society (Nov 2017), £15,000
Hannah Dugdale, Royal Society (Nov 2017), £15,000
Shaunna Burke, Cancer Research UK Innovation Grant (Nov 2017), £20,000
Alex O'Neill and colleagues in Chemistry, BBSRC (Nov 2017), £431,865
Jessica Kwok, Wings for Life (Nov 2017), £87,365
Tom Bennett, BBSRC (Oct 2017), £523,679
Neil Ranson, Darren Tomlinson, BBSRC (Oct 2017), £494,318
Nikita Gamper, BBSRC (Oct 2017), £490,426
Amanda Bretman and colleagues from UEA, NERC (Oct 2017), £430,886
Juan Fontana, Rosetrees Trust consumables grant (Oct 2017), £22,500
Helen Miller, DSM Nutritional Products AG (Sep 2017), £69,988
Neil Ranson, Juan Fontana, Mark Harris, Michelle Peckham, Ralf Richter, Peter Stockley, Patricija Van Oosten-Hawle and colleagues in Engineering, FMH and MAPS, Wellcome Trust Equipment Call (Sep 2017), £418,000
Jamie Johnston, Physiological Society (Sep 2017), £10,000
Frank Sobott, Adrian Goldman, Mark Harris, Andrew Macdonald, Stephen Muench, Sheena Radford and colleagues in FMH and MAPS, Wellcome Trust Equipment Call (Aug 2017), £415,000