There are ten members of the TMEM16/Anoctamin family of proteins in mammals. Although the first members of this family to be discovered, TMEM16A and TMEM16B, have a calcium-regulated chloride channel function, subsequently other members of the family, such as TMEM16F, were found to have lipid scramblase activity combined with non-selective ion channel activity. TMEM16K was a relatively understudied member of the family despite the observation that mutations in TMEM16K have been linked to the genetic disease autosomal recessive spinocerebellar ataxia Type 10 (Also known as SCAR10 or ARCA3).

The TWIK related acid-sensitive K⁺ channel 1 (TASK-1) belongs to the family of two-pore domain potassium (K_2P) channels. It regulates resting membrane potential and is expressed in cardiomyocytes, neurons and vascular smooth muscle cells.

The folate and methionine cycles are essential metabolic pathways for life, involved respectively in DNA synthesis and generation of the ubiquitous methyl donor S-adenosylmethionine (SAM). The enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR) represents a key regulatory connection between these cycles, hence exerting a strong influence on an array of diseases. This TEP presents the first structures for any eukaryotic MTHFR, revealing a novel SAM-binding fold.

Erythorid specific 5’-Aminolevulinate synthase (ALAS2) catalyses the first and rate-determining step in haem biosynthesis during erythroid development.

We have cloned, expressed, purified and crystallised the first DH GEF domain of Kalirin (gene: KALRN) in complex with RAC1 (gene: RAC1) as part of a programme to explore a new way of targeting GTPases. Fragment screening and X-ray crystallography has identified binders within the orthosteric binding site. A nucleotide exchange assay has been developed and GEF activity established.