Oliver Thorn-Seshold

Chemistry World was delighted to sponsor a poster prize at ISACS16 (Challenges in Chemical Biology), held in Zurich, Switzerland, last month. Oliver Thorn-Seshold was the winner with his poster entitled ‘Photoswitchable inhibitors of microtubule dynamics: Photostatins optically control mitosis and cell death.’

Oliver explains his work:

‘My motivation was to take a shot at curative tumour chemotherapy, based on a mechanism that has not been explored for drugs before – reversibly light-targetable cytotoxins.

The idea is to apply the drug globally in the patient, but activate it locally in the tumour by illuminating the tumour zone with pulses of blue light. Outside the tumour zone, the drug should remain inactive. One could therefore use higher doses than conventionally possible, so therapeutic effectiveness can be improved whilst limiting side effects.

‘It turns out, that photostatins are a great proof-of-concept on the molecular level for this idea! Our initial photostatins can essentially be switched ON and OFF (and /ON/OFF/ON/…) – since the ON state is more than 250 times more toxic than the OFF state: this is about an order of magnitude more powerful than any switchable compounds shown before. We can reversibly toggle between those states inside living cells and tissues just by applying light or not – which is also a new step for the field. So we can set up spatially-defined toxicity – a proof-of-concept for tumour-site-selective therapy.’

Oliver got hooked on classical organic chemistry in high school, deviated into theoretical chemistry and optics during his degree at the University of Sydney in Australia, returned to focus on bioorganic chemistry for his PhD at the University of Lyon in France, then found a home in the Trauner research group at the University of Munich in Germany, where he combined his passion for organic synthesis, logic and modelling, light, and chemical biology, to work on photostatins in his current position as postdoc.

Oliver and his colleagues continue to work on tuning the light response of photostatins, using substituent pattern shifts for small changes as well as designing entirely different response regimes. This is aimed at sophisticated research applications, looking deeper into cell functions than current photostatins can do; and also to develop photostatins that can be controlled by red light in deep tissue settings.

The project itself began in 2012 when Thorn-Seshold ran out of funding for his PhD and couldn’t get an extension to finish it. So together with Gosia Borowiak, who was also finishing her PhD, they submitted cancer-targeting strategies to small funding calls and eventually scraped together three different funds to cover 75 days’ work.

‘We hit many problems, bridging chemistry and biology with optics, but I think having disjointed skills – I hadn’t even seen a cell under a microscope and Gosia’s last time in the chemistry lab was 10 years ago – worked out well, as by really working together we could do something new in chemical biology despite our total inexperience in each other’s fields.’

Thorn-Seshold and his colleagues have now published this research in the journal Cell.

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There’s still time to submit a poster abstract for ISACS18 (challenges in organic materials and supramolecular chemistry) to be held in Bangalore, India, in November. Winners will receive £250, a highly sought-after Chemistry World mug and a certificate.

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ISACS16 poster prize winner: Oliver Thorn-Seshold, 10.0 out of 10 based on 2 ratings
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