The origin of metabolism and heredity

This project is available from the academic year 2023/24 onwards.

Theme: Past Life & Environments

Primary Supervisor:

Nick Lane

Genetics, Evolution and Environment, UCL

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Secondary Supervisor:

John Ward

Biochemical Engineering, UCL

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Project Description:

Life hydrogenates carbon dioxide to form organic molecules. In cells this difficult process is facilitated by membrane bioenergetics – steep pH gradients modulate reduction potentials of H2, CO2 and iron-sulfur proteins to drive intermediary metabolism. Geochemical environments can provide steep pH gradients and FeS clusters, allowing each step of protocell evolution to maintain an equivalent topology to modern cells. We hypothesise that the structure of metabolism in cells is determined by vectorial energy flow. The lab is working on a range of questions, in particular: (i) testing the vectorial reduction of CO2 by H2 to form carboxylic acids, amino acids, sugars and nucleotides from biologically meaningful precursors in a microfluidic reactor or under a wider range of conditions; (ii) simulating the origins of metabolism by computational modelling and empirical testing of predictions in protocells, notably the behaviour of FeS clusters associated with membranes; and (iii) considering the emergence of genetic heredity in protocells, linked with nucleotide synthesis and polymerization, driven by activated phosphates such as acetyl phosphate, to explore how the universal code might be grounded in a genetic takeover structured by metabolism.

Within this broad remit, the student will have plenty of scope for flexibility to match their interests, ranging from computational modelling to prebiotic syntheses or protocell behaviour.

Policy Impact of Research:

The origin of life is a major unsolved problem in science.
This project pioneers an experimental, computational approach that could provide concrete answers, with implications for energy security and global warming: proton gradients could drive the reduction of CO2, combining carbon capture with production of synthetic gasoline.

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