Cysteinolic Acid Metabolism in Marine Algae and its Fate in Humans

An exciting new Structural and Chemical Biology PhD opportunity exists to discover new pathways for the degradation of sulfur-containing marine metabolites and enzymes for their utilization in humans. This project will be hosted jointly between the Universities of Manchester and Melbourne.

The element sulfur is required for the growth and existence of all living organisms. Sulfur forms a diverse array of small organo-sulfur molecules connected through complex chemical networks that allow the “cycling” of sulfur in our environment. This process is known as the sulfur biogeochemical cycle, and is crucial due to its significance in agriculture, food production, and carbon dioxide uptake. Despite this, many of the main chemical species are poorly studied with little known about their biosynthesis or degradation. The discovery of missing links in these biochemical pathways will transform our understanding of the natural world. This project will discover and characterize new pathways and enzymes involved in the biogeochemical sulfur cycle. It will involve synthetic organic chemistry, biochemistry, and structural biology.

The project seeks to answer the following questions:

• What is the distribution of cysteinolic acid in diverse marine alga?
• What is the pathway used by marine microbes to break down cysteinolic acid?
• What is the distribution and occurrence of degradative pathways for cysteinolic acid in marine ecosystems?
• Can cysteinolic acid be metabolized into bile salts by human liver conjugation enzymes?

The candidate will be based in Manchester and will spend one year at the University of Melbourne. The project will discover and characterize new biochemical pathways and enzymes for breakdown of cysteinolic acid, an abundant yet currently enigmatic organosulfur metabolite, and will enrich our understanding of how organosulfur molecules support marine ecosystems and contribute to food webs. The project will involve synthetic chemistry, biochemistry and structural biology. The candidate will synthesize novel organosulfur metabolites and use these to discover new degrader organisms, and the molecular basis for their breakdown. Working in Manchester, the candidate will undertake biophysical characterization and structural studies on newly identified proteins.

The project will utilize state-of-the-art instrumentation including nuclear magnetic resonance, high-resolution mass spectrometry, isothermal titration calorimetry, size exclusion chromatography multi-angle light scattering, and analytical high-performance liquid chromatography-mass spectrometry, and will be exposed to an exciting inclusive, collaborative, international research environment.

Supervision team

The University of Melbourne:

Professor Spencer Williams

Professor Laura Burchill

The University of Manchester:

Dr Yi Jin

Professor Robert Field

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Further details