Synthesis and utilisation of biochemical tools to investigate fatty acid and lipid metabolism

合成一系列新型甘油和脂肪酸类似物/衍生物，作为研究快速分裂细胞（如寄生虫）中脂肪酸和脂质代谢的工具。这些将被用于它们在原生动物寄生虫和哺乳动物细胞中的吸收和利用。该学生将从事各种天然产物基序的各种类型的化学合成，包括制造一系列类脂分子和甘油类似物，作为研究其代谢的新工具，以了解一般的脂质代谢。该学生将研究甘油和脂肪酸类似物/衍生物的吸收和利用，无论是作为能源，还是将其纳入脂质膜，这可能会改变其生物物理特性，破坏正常的细胞功能和过程。这包括脂肪酸延伸，脱氢，以及脂肪酸的β -氧化。甘油和脂肪酸类似物/衍生物还将用于探索针对特定酶的结构活性关系，这些酶先前已被该小组验证为引起被忽视的热带病的各种原生动物寄生虫的药物靶点。学生将接受Cat 3水平的全面培训，进行寄生虫和哺乳动物细胞培养和生化操作。这将允许他们进行EC50值测定和生化表型分析。学生随后将合成和利用其最佳命中的新型亲和探针，以确保“瞄准”和行动模式的研究。

Synthesis a range of novel glycerol and fatty acid analogues/derivatives as tools to investigate fatty acid and lipid metabolism in fast dividing cells, i.e. parasites. These will be utilised to their uptake and utilisation in protozoan parasites and mammalian cell.The student will be undertaking various types of chemical synthesis of various natural product motifs, including making a range of lipid-like molecule and glycerol analogues as novel tools to investigate their metabolism to inform about general lipid metabolism.The student will investigate the uptake of and utilisation of glycerol and fatty acid analogues/derivatives, either as energy sources, or their incorporation into lipid membranes which may alter their biophysical properties, disrupting normally cell functions and processes. This includes fatty acid elongation, dehydrogenation, as well as beta-oxidation of fatty acids.The glycerol and fatty acid analogues/derivatives will also be utilised to explore structure activity relationships against specific enzymes, which have been previously validated as drug targets by the group for various protozoan parasites that cause neglected tropical diseases. The student will be fully trained at a Cat 3 level to undertake parasite and mammalian cell culture and biochemical manipulations. This will allow them to undertake EC50 value determinations and biochemical phenotyping. The student will subsequently synthesise and utilize novel affinity probes of their best hits, to ensure "on-target" and mode of action studies.