Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

People with depression often receive treatment with antidepressant medications such as selective serotonin reuptake inhibitors (SSRIs). SSRIs produce activation of all types of serotonin receptors and some of these receptors are thought to mediate side-effects rather than the therapeutic effect of SSRIs. Also activation of certain other serotonin receptors may delay the onset of therapeutic action of the SSRI treatment. Animal experimental studies have suggested that the 5-HT4 serotonin receptor may be important in mediating the antidepressant effects of SSRIs and targeting this receptor directly may work more quickly than conventional SSRI treatment. Carrying out large-scale clinical trials of new agents in depressed patients is costly and time consuming and therefore one would only want to pursue this approach when there was supporting evidence from experimental medicine studies in humans that 5-HT4 receptor drugs may well be useful in depression. We have developed models of emotional processing (psychological tests that measure how people respond to emotional stimuli) that can detect potential antidepressant effects of novel compounds after only a few days of treatment. We therefore plan to use these models to see whether a new drug that selectively activates 5-HT4 receptors can produce antidepressant-like changes in emotional processing after just one week of treatment. We will carry out these studies in two separate groups of depressed patients: first, those who are not taking any antidepressant medication and second, people who have not experienced a good response to their current treatment. Both these clinical situations are where advances in drug treatment are badly needed. Positive results from one or both of these studies will lead on to formal clinical trials of a 5-HT4 receptor agonist drug in depressed patients.

Doctoral Training Partnerships: a range of postgraduate training is funded by the Research Councils. For information on current funding routes, see the common terminology at https://www.ukri.org/apply-for-funding/how-we-fund-studentships/. Training grants may be to one organisation or to a consortia of research organisations. This portal will show the lead organisation only.

Doctoral Training Partnerships: a range of postgraduate training is funded by the Research Councils. For information on current funding routes, see the common terminology at https://www.ukri.org/apply-for-funding/how-we-fund-studentships/. Training grants may be to one organisation or to a consortia of research organisations. This portal will show the lead organisation only.

Fluorinated molecules have risen to the forefront of modern scientific advances. From Teflon to pharmaceuticals (including blockbuster drugs, e.g. Lipitor), the controlled formation of carbon-fluorine bonds has imparted revolutionary biological and structural effects. However, the current methods to form carbon-fluorine bonds generally rely on highly reactive fluorine sources that limit widespread application and use. This grant will develop fluorine sources based on boron-fluorine bonds that enable the formation of carbon-fluorine bonds using new and orthogonal reactivity to current methods. Boron offers a sustainable choice for catalysis with low physiological and environmental toxicity. This makes it an ideal choice for applications in the pharmaceutical and agrichemical sectors. The boron-fluorine bond is usually considered to be relatively inert, but our deep understanding of boron chemistry will enable the reactivity of B-F bonds to be switched on. This project will achieve this by rationally tuning the structure about boron to enable the capture of fluorine from simple, inexpensive stable sources (e.g. MF) and subsequently transfer it to simple and complex molecular frameworks. Three methods to do this have been identified: 1. Phase-transfer Catalysis; 2. Fluorine transfer and trapping of activated substrates; 3. Transfer of fluorine and boron to unactivated substrates. These methods share a common theme of boron-fluorine bond formation and subsequent fluorine transfer, but they are not inter-reliant. Each method will be developed separately and addresses a different synthetic need. Phase-transfer catalysis will take fluorine from the solid or aqueous (water) phase and transfer it to the reactive, organic phase. The structure about boron will be used to control the position and facial selectivity of the transfer. Fluorine transfer to activated and unactivated substrates will exploit an activated boron-fluorine bond. Key to this will be activation of the boron-fluorine bond on approach to the substrate and the structure about boron will be used to enhance this interaction and ensure boron-fluorine bond activation. All three methods will be used to explore and understand the fundamentals of boron-fluorine bonding, how to effect high yielding fluorine transfer to substrates, and how rational modifications to borane structure can be used to enable new reactivity. All of the methods will culminate in the application of the new reactivity to industry relevant targets - new active pharmaceutical ingredients, agrichemicals and materials precursors.