Live cell super-resolution microscopy assessment of novel ratiometric luminescent transition metal complexes.

This proposal is aimed at strengthening and providing the all-important next milestone in the current ongoing collaboration between the applicant and Dr. Filip Kielar, Naresuan University, Phitsanulok, Thailand. The collaboration is based on the Dr. Filip Kielar's expertise in the field of transition metal complexes and the expertise of Dr. Robert Pal in optical microscopy and associated live cell imaging and time-resolved spectroscopy. Due to the unique nature of transition metal complexes, such as longer fluorescent lifetime as opposed to short lived tissue auto-fluorescence and their potential application as photoinduced singlet oxygen generators, their in cellulo application is of great interest. We propose to study these newly synthesized compounds that can report on key biologically important analytes in live-cell studies using a variety of optical techniques, such as Laser Scanning Confocal-, Time-resolved- and Fluorescent Life Time imaging Microscopy.

This collaboration was initially established as a result of a Royal Society International Exchange Scheme grant in 2014 that was awarded to Dr. Pal and Dr Kielar allowing them to engage in collaborative work. The scheme, being a travel only grant, allowed them to conduct a 2 week long visit each, facilitating all-important face to face meetings and discussions to shape and drive the project forward maximising scientific output and delivering under and post graduate lectures. Exactly one year and lots of hard work later we were in the fortunate positon, that our collective findings have been published in Dalton Transactions (2016, 45, 17420). As a result of this well-oiled collaboration a further more extensive Thai Research Fund grant was submitted in 12/2016 to facilitate the synthesis of the next generation of complexes to be studied at Durham (awarded to Dr. Kielar, commenced 02/2017 with no travel allowance for the PI). However, the above mentioned grant only facilitates research staff (3 year PhD) and consumables cost to be met at Naresuan University. Dr. Pal has already earmarked the continuation of this project as a dedicated 2017/18 MSc. student.
Researchers at Narressuan University are extremely happy with our preliminary fruitful collaborative work and communications on this subject, and truly believe that due to the expertise and dedication at Durham we have achieved so much in so little time on this subject despite the logistics originating from our very different geological and financial position.

Manufacturing the future is a core area identified for support by EPSRC. The overarching scientific aim, the development of novel responsive luminescent chemical entities that could report on biologically important species, such as local analyte concentrations and environmental parameters (e.g. pH, pCO2) without perturbing natural cell homeostasis is extremely timely as they could aid cutting edge bio-medical research by providing a robust non-invasive detection or monitoring system. The PI has both the capacity and track record in delivering impact but it will be the responsibility of all members of the collaborative research team to do so. Impact activities will be subsidised through existing University funds. Durham has an excellent track record in maximising impact. Notably, in REF2014 Durham Chemistry research was rated as having the highest impact within the UK (76% rated 4*).

The proposed project has already drawn attention from potential academic, industrial and commercial partners. The preliminary results have been published in Dalton Transactions (2016, 45,17420). The PI, is at an early stage of his career, yet already has extensive experience in working with industry and in the development and exploitation of novel IP (2 spin-out companies, FScan and PB Spectroscopy Ltd - both non-stipendiary positons, 6 patents). Durham University is committed to facilitating the translation of fundamental research into successful commercial entities. The technology transfer team at Durham will help to evaluate project impact and assist in industrial engagement (i.e. preparation of MTA and NDA/CDA agreements).

The proposed visit would allow the PI from Durham to visit the synthetic lab in Phitsanulok Thailand, where based on his expertise a small optical microscopy facility is proposed to be set up to conduct any initial cellular assessment of these novel luminescent transition metal complexes. This would not only aid initial assessment of active compounds to be undertaken, but subsequently would maximize scientific output in an extremely time efficient manner. The visit would also facilitate the finalization of discussions of our follow on paper for publication and a pipeline future grant submission that would allow the expansion of this research at both research institutions bearing great scientific merits.
The aim, once a mutually beneficial meeting is facilitated, is that the proposed project will be further exploited and based on our current and future findings this drafted large proposal will submitted to relevant funding bodies as an extensive fully costed potentially 2-3 year project supporting a post-doctoral researchers with Dr. Pal as PI. Upon successful further funding capture we foresee the translation of our research into a portable demonstration kit to be used for public engagement. The PI and his research group are committed and active members with an extensive track-record. The public engagement activities will include the use of social media to inform the public of the progress of the project and highlighting the research at public events (e.g. Royal Society Summer Science Fair, British Science week, Museum Lates). These events typically feature examples from EPSRC-funded projects and receive excellent feedback. Our aim is not only to educate and inspire the next generation of scientists but also raise the public's awareness of our research. These activities also present to school students the diverse career possibilities open to researchers working across the life sciences, leading to future participation in these areas (e.g. undergraduate degree studies in the life or physical sciences).