|Salary:||£34,304 to £40,927|
|Placed On:||23rd November 2021|
|Closes:||5th December 2021|
The identification of carbon dioxide-binding proteins
Carbon dioxide is essential for life. It is at the beginning of every life process as a fundamental substrate of photosynthesis or chemosynthesis and is at the end of every life process as the product of aerobic respiration and post-mortem decay. As such, it is not a surprise that this gas regulates such diverse processes as cellular chemical reactions, transport, maintenance of the cellular environment, behaviour and immunity. Carbon dioxide is a strategically important research target with relevance to crop responses to environmental change, insect-borne disease and public health. However, we know very little of the direct interactions of carbon dioxide with the cell, despite the importance of the gas to biology.
Carbon dioxide mediates the earliest known example of a protein post-translational modification (PTM), identified on haemoglobin in 1928. Carbon dioxide can directly combine with select protein groups to form carbamates. Influential research programmes from the 1920-80's demonstrated that the carbamate PTM regulates oxygen-bin! ding in h aemoglobin and activates the carbon dioxide-fixing enzyme Rubisco. George Lorimer proposed carbamate PTMs as a mechanism for regulating biological responses to carbon dioxide in 1983. However, the carbamate PTM is unstable outside the cell and its identification presents significant analytical challenges. Several stable carbamates have been identified in protein molecular structures, but the technical difficulties in their widespread identification has resulted in carbon dioxide-mediated carbamylation being all but forgotten as a PTM. For example, the Wikipedia page for PTM does not mention carbon dioxide-mediated carbamylation (not to be confused with the similarly named modification mediated by isocyanic acid) among 61 identified PTMs.
Direct protein targets for carbon dioxide sensing are almost completely unknown. We have developed technology to systematically identify carbon dioxide-binding proteins. We propose to understand the diversity of carbon dioxide-binding proteins in a mammalian proteome and demonstrate biological relevance. The research programme! will pro vide our first broad insight into direct molecular responses to carbon dioxide and supply tools that will revolutionise our understanding of carbon dioxide biology.
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