About 15% of the population have health problems due to arthritis and other associated conditions. The most common type of arthritis is osteoarthritis. The main reason why people with osteoarthritis go to see a doctor is pain. Pain is also the main reason why people with osteoarthritis lose their mobility. However the type of treatments available for people with osteoarthritis are very limited. Our research group has carried out studies that have shown that pain from osteoarthritis has an emotional effect on the brain that affects how pain is felt. This emotional effect could make a big difference to how patients respond to treatment or surgery. By reducing the effects of these emotions we could reduce how unpleasant the pain feels. This could also help to keep more people mobile. Our research aims to investigate how emotions such as anxiety and distress which affects how we feel pain, are altered by the natural painkillers made by the brain (opiates). We would like to approach people with osteoarthritis and ask them to take part in our study. Specifically, we would like to test a variety of people with different levels of anxiety and distress. We will make use of techniques that can produce images of the brain to measure the naturally occurring brain opiates, and how they affect how we expect (anticipate) and feel (give attention to) pain. These studies will help us explain how different people experience pain and why they respond differently to treatments. In the long term, they will also help us understand how the brains own painkillers work, and how we can improve on existing treatments for pain from osteoarthritis and also develop new therapies.

The palate (the roof of the mouth) develops from two distinct parts that fuse together during development of the baby. Currently, we do not completely understand what controls these events, but we do know that the common and distressing birth defect cleft palate results when fusion of the two halves of the palate fails to occur. Patients with cleft palate experience difficulties with eating and speaking, which can be corrected to some degree by long-term surgery, dental treatment, and speech therapy; it is therefore essential that we have more information on how genes work together during normal development and how these are affected in cleft palate. The aim of this project is to study the way in which two genes, designated p63 and IRF6, function together during development of the palate. So far, we have discovered that p63 switches on the function of IRF6 and that this, in turn, causes the levels of p63 to drop just before fusion of the two halves of the palate. In our initial studies, we will determine whether or not cleft palate results when p63 is maintained at an artificially high level in the palate of developing mice. Subsequently, we will obtain a more complete picture of the ways in which the palate develops by discovering the target genes controlled by p63 and IRF6. In the short-term, this research will help us to understand the processes that underlie normal development of the palate and how these are disrupted in cleft palate. In the longer term, this information may help us to provide improved genetic diagnosis and counselling to patients and their families who are affected by this distressing condition.

The palate (the roof of the mouth) develops from two halves that fuse together during embryonic development. Currently, we do not completely understand what controls these events, but we do know that the common and distressing birth defect cleft palate results when fusion of the two halves of the palate fails to occur. Patients with cleft palate experience difficulties with eating and speaking, which can be improved to some degree by long-term surgery, dental treatment, and speech therapy; it is therefore essential that we have more information on how genes work together during normal development and how these are affected in cleft palate. The Sonic Hedgehog protein is a key molecule in ensuring that the palate develops normally; however, only a small fraction of proteins acting in response to Sonic Hedgehog has been identified. Recently, methods have been developed that will allow us to identify the complete set of proteins controlled by Sonic Hedgehog. We will use these techniques to dissect the role of Sonic Hedgehog signalling in ensuring that the palate develops correctly thereby preventing cleft palate. To ensure that this research is completed ethically, we will perform these experiments in mice, in which the palate develops in exactly the same way as in humans. In the short-term, this research will help us to understand the processes that underlie normal development of the palate and how these are disrupted in cleft palate. In the longer term, this information will help us to provide improved diagnosis, genetic counselling and treatment to patients and their families who are affected by this distressing condition.

This proposed research explores the adaptation and reconceptualisation of Shakespeare in contemporary Iranian theatre between 2000 and 2020. Overall, Iranian Shakespearean reworkings pursue three main approaches: (1) the plays that challenge important political issues such as the establishment of dictatorship in modern history of Iran, the Hamlet and Macbeth adaptations in particular; (2) the plays that engage in reflecting on Iran's sociocultural problems such as gender inequality and theatre censorship; and (3) the reworkings that spark philosophical-aesthetic discussions aiming at practicing an experimental stage against perception and meaning in the mainstream theatre. By using cultural materialist dissident reading and adaptation studies, as well as sociopolitical criticism, this proposed research analyzes adaptation politics, the scope of dissidence, and the way Iranian adapters have utilised Shakespeare in productive and engaging ways to reflect on sociocultural, political and philosophical issues in present-day Iran. Contemporary Iranian historical events such as civil uprisings since 2000s are deciding factors in the emergence of social, political and alternative interpretations and adaptations of Shakespeare in playwriting practice and theatre production in Iran. Significantly, this project seeks to introduce and examine Iranian political playwriting and the prominent yet little-known Iranian playwrights to global academic audiences. Although there is a body of scholarship on Shakespeare and the Arab world (e.g. Al-Shetawi, Hennessey and Litvin), there is minimal scholarship on Shakespearean adaptations in Iran, especially since the 2000s. To this end, my proposed project aims to make a significant contribution to Global Shakespeare Studies by investigating and evaluating the reception, influence, and political use of Shakespeare in the context of contemporary Iran. It also advances adaptation theory by extending its theorization and application to the mutual interplay between the Western canon and literatures of so-called Third World countries, including Iran. Working with this theoretical framework, my proposed doctoral thesis will raise and attempt to answer the following research questions: 1. What possibilities has Shakespearean adaptation offered for political intervention in the Iranian context? 2. In what way has the post-Revolutionary context inspired Iranian playwrights to engage in adaptation and appropriation playwriting? 3. What possibilities have rewritings of Shakespeare by Iranian playwrights offered for contemporary spectacle? 4. What are the impacts of theatre censorship on Iranian drama? In what way have Iranian adaptations addressed this issue through adaptations?

Pre-eclampsia and fetal growth restriction (babies born smaller than they should be) are complications that affect up to 1 in 10 pregnancies and are responsible for grave illness in affected mothers and babies. Each year in the UK, up to 5 women and 600 babies die because of pre-eclampsia; 1 in 4 stillbirths are caused by fetal growth restriction and this is responsible for 1 in 6 sudden infant deaths. Babies who survive these complications are at greater risk of cerebral palsy and, later on in life as children and adults, they are at higher risk of suffering heart disease, diabetes, bone disease and mental health problems. Babies born of pregnancies complicated by pre-eclampsia and fetal growth restriction place a heavy burden on the NHS, with 20% of all intensive care baby cots being occupied by babies from pre-eclampsia pregnancies and around #420m being spent each year on intensive care of growth restricted babies. In addition, looking after children with illnesses related to pre-eclampsia and fetal growth restriction places a heavy burden on families, the NHS and social services. Unfortunately, there are no cures for either pre-eclampsia or fetal growth restriction and women suffering from severe problems have to undergo premature delivery of their baby, which also carries great risks of chronic illness and death. Although there have been no drugs specially designed to treat these illnesses, there are a number of possible treatments that are used to treat other illnesses and that have already been shown to be safe in people who are not pregnant. These treatments cannot be tested on pregnant women without first establishing whether they are effective and safe in treating symptoms of pre-eclampsia and fetal growth restriction in animals. We would like to test a number of existing drugs to see if they are useful at treating the symptoms of these diseases in a number of specially-bred mouse strains that display signs of pre-eclampsia and fetal growth restriction when pregnant. Once we have found which treatments have the greatest potential for treatment in mice, we will use them on blood vessels taken from human placentas and women (with informed written consent) after they have given birth to test whether they might be effective in human pregnancy. Such experiments will provide information on how to design clinical trials for the development of these treatments in pregnant women suffering from pre-eclampsia or fetal growth restriction.