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Department of Chemistry

Dr Robert Pal

Assistant Professor in the Department of Chemistry
Telephone: +44 (0) 191 33 42102

(email at robert.pal@durham.ac.uk)

Molecular Nanomachines

This is one of our flagship research areas in collaboration with Prof. James M. Tour, Rice Univeristy, Houston, Texas (USA). 

Using a new generation of light activated cell type specific molecular nanomachines we have demonstrated the use of molecular mechanical action to open cellular membranes and lipid bilayers and expedite cell death in a fully controlled manner. The efficacy of this method using single photon excitation in the UV domain was demonstrated and has been recently published in Nature (2017, 548, 567-572).

Our overarching future aim is to extend our study beyond in vitro applications. Using UV light to activate these molecular machines in vivo has signification limitations associated with shallow tissue penetration and potential UV damage. In order to overcome this we propose to extend our research into the two-photon-, near-infrared activated domains.

Our vision for the future is to develop and validate a series of light-activated molecular machines to selectively target cancerous cells in the human body and safely eradicate them, in order to pave the way to the development of a fundamentally new photodynamic therapy protocol combining cell type and metabolic/morphological state specific uni-molecular nanomachines and biologically safe near infra-red activation. Once fully developed and validated it could be potentially adopted as a new form of extremely high 3D optical precision, facile and non-invasive Type V photodynamic therapy to eliminate the need of currently used highly invasive surgical or radiotherapeutic procedures that often harmful to administer.

https://www.youtube.com/watch?v=UE_Zh8XUDuE

 

https://www.facebook.com/playgroundenglish/videos/526788354321166/?hc_ref=ARSiru6KXoz61OCuYDnCcQrDv1cpvTNd0AsD-30YqJHfvkPwBYUWPO552LFvqVrlX8A&pnref=story

Biography

Robert Pal grew up in Hungary and graduated from KLTE University of Debrecen, in 2004. Once completing his undergraduate studies he has moved to Durham to start a Ph.D with Professor David Parker on Responsive Luminescent Lanthanide systems. Completing his Ph.D in late 2007 he began to work as a Postdoctoral researcher within the Parker group, also working closely with Professor Andrew Beeby, moving away from organic chemistry towards bio-physical chemistry, spectroscopy and microscopy. In 2014 he has been awarded with a prestigious University Research Fellowship from the Royal Society to study the Development and Chemical Application of Phase Modulation Nanoscopy.

Robert is also the Technical Director of a successful University spin out company, FScan Ltd, which has developed lanthanide technology to be used as part of a novel test for Prostate Cancer detection that is currently part of an ongoing clincial trial. 

He has also founded PB Spectroscopy limited alongside Prof. Andrew Beeby, a company that is dedicated for the development of miniaturised and affordable spectroscopic instrumentation and solutions.

Research Interests

RP is a physical chemist working on the border of organic chemistry and biophysics with expertise in lanthanide based sensors and cellular probes. In recent years he has focused his main research interest on innovation in the development of bespoke optical instrumentation, notably for high resolution, affordable microscopy and in portable optical spectroscopy for emission and circular polarised luminescence. In addition he also strives to capitalise on his new research interest in targeted light activated molecular nanomachines (Nature 2017).

Super-resolution Microscopy or ‘Nanoscopy’

 'A picture is worth more than 100 words' 

 'A picture is worth more than 100 words'

In the field of optical fluorescence microscopy, many researchers have dedicated their entire scientific carrier to develop better and improved cellular stains or associated microscopy techniques and equipment, pushing the boundaries of both signal detection and resolution. However, the intrinsic resolution of fluorescence microscopy is limited by diffraction, which determines the extension of the focused light emitted by a point source object, in other words the point spread function (PSF). In recent years, renewed have efforts emerged in optical microscopy and associated life sciences to break through the optical diffraction barrier and visualize even smaller parts of the ‘living’ cell in ‘super-resolution’. Governed by Abbé’s law (1873) the highest achievable theoretical spatial resolution (d) of a given experimental setup is dictated by the lowest applied excitation light (λexc) d = λexc./2NA (NA: numerical aperture of objective) promoting maximal achievable resolutions of ~200 nm. However, much of the fundamental biology of the cell occurs below this threshold; hence breaking this limit will allow the wide multidisciplinary scientific community to look deeper in higher resolution.

Ever since the step-changing invention of Confocal Microscopy by Minsky in 1953, attention has turned towards the development of new optical (hardware) and computer (software) based methodologies, revolutionising the way in which we investigate nanostructures. Recent years seen many refined and evolved variants of ‘Super-resolution’ techniques by improvements applied either or both to the illumination or detection process leading to improvement in both precision and resolution. No need to say this combined multidisciplinary effort have recently been recognised with the Nobel-prize awarded in Chemistry in 2014. But these new, still fundamentally diffraction limited techniques all have drawbacks too, such as limitation of suitable stains, disruptively high laser powers, slow/limited imaging speed, poor SNR due to loss of information and specialized expensive and bulky instrumentation.

Taking the above into account, the obvious conclusion for me is to introduce novel user friendly resolution enhancing methods (both hard- and sofware) into existing microscope platforms, on what several members of our research group is working on.

Publications

Journal Article

Newspaper/Magazine Article