Membrane adaptation under pressure

Lead Research Organisation: Imperial College London
Department Name: Chemistry

Abstract

Oceans cover over 71% of Earth's surface at an average depth of 3800 metres and it is remarkable that we still discover hundreds of new species of marine life with every exploration. Life continues to thrive in the ocean trenches which are up to 11 km deep where organisms have to cope with pressures of 1100 bar. The adaptation mechanisms that enable organisms to survive these crushing pressure remain elusive.
Given the extreme pressure in the deep sea, how can organisms cope with such crushing forces? Much like a chameleon changes colour to match it environment, high pressure tolerant organisms are able to modify their molecular make-up to ensure that they remain functional (e.g. their membranes must remain fluid and not crystallise), however, the mechanisms behind this adaptation and the parameters that are regulated remain elusive. This is primarily due to the fact that the laboratory culture of extreme barophiles and the development of analytical high-pressure apparatus is non-trivial. During this project we will develop instrumentation to study barophiles at pressures found in the deepest oceans on Earth and use this to monitor key biomechanical signatures as a function of pressure.

Planned Impact

Addressing UK skills demand: The most important impact of the CDT will be to train a new generation of Chemical Biology PhD graduates (~80) to be future leaders of enterprise, molecular technology innovation and translation for academia and industry. They will be able to embrace the life science's industrialisation thereby filling a vital skills gap in UK industry. These students will be able to bridge the divide between academia/industry and development/application across the physical/mathematical sciences and life sciences, as well as the human-machine interfaces. The technology programme of the CDT will empower our students as serial inventors, not reliant on commercial solutions.
CDT Network-Communication & Engagement: The CDT will shape the landscape by bringing together >160 research groups with leading players from industry, government, tech accelerators, SMEs and CDT affiliates. The CDT is pioneering new collaboration models, from co-located prototyping warehouses through to hackathons-these will redefine industry-academic collaborations and drive technology transfer.
UK plc: The technologies generated by the CDT will produce IP with potential for direct commercial exploitation and will also provide valuable information for healthcare and industry. They will redefine the state of the art with respect to the ability to make, measure, model and manipulate molecular interactions in biological systems across multiple length scales. Coupled with industry 4.0 approaches this will reduce the massive, spiralling cost of product development pipelines. These advances will help establish the molecular engineering rules underlying challenging scientific problems in the life sciences that are currently intractable. The technology advances and the corresponding insight in biology generated will be exploitable in industrial and medical applications, resulting in enhanced capabilities for end-users in biological research, biomarker discovery, diagnostics and drug discovery.
These advances will make a significant contribution to innovation in UK industry, with a 5-10 year timeframe for commercial realisation. e.g. These tools will facilitate the identification of illness in its early stages, minimising permanent damage (10 yrs) and reducing associated healthcare costs. In the context of drug discovery, the ability to fuse the power of AI with molecular technologies that provide insight into the molecular mechanisms of disease, target and biomarker validation and testing for side effects of candidates will radically transform productivity (5-10 yrs). Developments in automation and rapid prototyping will reduce the barrier to entry for new start-ups and turn biology into an information technology driven by data, computation and high-throughput robotics. Technologies such as integrated single cell analysis and label free molecular tracking will be exploitable for clinical diagnostics and drug discovery on shorter time scales (ca.3-5 yrs).
Entrepreneurship & Exploitation: Embedded within the CDT, the DISRUPT tech-accelerator programme will drive and support the creation of a new wave of student-led spin-out vehicles based on student-owned IP.
Wider Community: The outreach, responsible research and communication skill-set of our graduates will strengthen end-user engagement outside their PhD research fields and with the general public. Many technologies developed in the CDT will address societal challenges, and thus will generate significant public interest. Through new initiatives such as the Makerspace the CDT will spearhead new citizen science approaches where the public engage directly in CDT led research by taking part in e.g hackathons. Students will also engage with a wide spectrum of stakeholders, including policy makers, regulatory bodies and end-users. e.g. the Molecular Quarter will ensure the CDT can promote new regulatory frameworks that will promote quick customer and patient access to CDT led breakthroughs.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/S023518/1 01/10/2019 31/03/2028
2600915 Studentship EP/S023518/1 02/10/2021 02/10/2025 Yifei LIAO