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.

We are dissecting the molecular mechanisms that control formation and maintenance of blood/haematopoietic stem cells (HSCs) in zebrafish embryos. In vertebrates, HSCs form during embryogenesis. In adult humans, they reside in the bone marrow from where they replace short-lived mature blood cells throughout life. Thus, they are essential for our survival. They are the active component of bone marrow transplants that are used to re-establish blood formation (haematopoiesis) in patients that have lost their blood system due to blood disorders, accidents or medical treatments. To develop new therapies, we need to be able to generate HSCs in vitro and to maintain and expand their numbers. To date, we know little about the molecular mechanisms that control these processes. We study zebrafish embryos with the aim to reveal these mechanisms. While we can identify the earliest potential HSCs by gene expression, we currently lack an assay to test them. Therefore, we are generating a transgenic fish line in which these cells express a green fluorescent protein. Fluorescent cells will be transplanted from a transgenic to a wild-type embryo to see whether they participate in long-term haematopoiesis. This assay will be an invaluable tool for dissecting the molecular mechanisms that control HSC biology.

Asthma is a disease that affects the airways that carry air in and out of the lungs. During an asthmatic attack, triggered by irritants such as dust or smoke, the muscle cells that line the walls of the airways, contract and tighten so that the airway becomes narrower. The lining of the airways becomes inflamed and sticky mucus or phlegm is produced. All these reactions cause the airways to become narrower and irritated - leading to the symptoms of asthma such as coughing and wheezing. Over time, repeated episodes of asthma can cause the number of muscle cells to increase resulting in the airway wall getting thicker. There is currently no cure for asthma, and although it can be managed with regular medication, complications can still arise. Considerable research is currently being undertaken to identify the factors that cause asthma - from genetic to environmental factors. Other research is aimed at understanding why asthmatic airways narrow so much and so fast, and at identifying the factors that cause the airway walls to thicken. Much of the research has been carried out on very specific aspects of the disease. For instance, one research group will look very closely at the chemicals that are released inside the muscle cell as a result of inhaling the irritant. Another group may focus on the components in the muscle cell that cause it to contract. Yet another group might look at how the muscle cells together (the tissue) responds to manipulations such as stretching. All these different things, however, interact during an asthmatic attack, but it is not easy to work out what the effect of these interactions are, just by looking at the individual measurements. The intention of this work is to create a new mathematical framework that combines physics, mathematics and biological information from on-going experiments. The research will bridge the gaps between the different levels (cells to tissues) as well as develop new models at each level. This framework will thus help us to understand how the processes involved in asthma interact with each other, and so to understand what might happen if we could disrupt one of the processes. For instance, does the mathematical model predict a lessening of symptoms? Or does it predict a shuffle-around of the interactions, thus compensating for the disruption? Answers to these important questions will help scientists move closer towards finding new, more effective, therapies.

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.

We aim to assess the impact of recent tobacco control policies on the number of smokers who succeed in stopping smoking in England. Smoking is the single greatest cause of preventable illness and premature death in the UK, and increasing the numbers of smokers who succeed in stopping smoking is the most important way of reducing morbidity and premature death in this country. This is the fundamental aim of many recent national tobacco policies. For example, larger and harder hitting health warnings have been introduced on cigarette packs. Financial incentives now encourage family doctors to help smokers who want to quit. Medications that aid smokers to quit, such as nicotine replacement products (NRT) have been made more accessible, for example, NRT can now be prescribed to adolescents and people with heart disease, and taxation has been reduced on over the counter sales of these treatments. Finally, a new treatment to help smokers quit has been launched, varenicline. How effective these policies and initiatives have been in increasing smokers’ attempts and success at quitting, and ultimately at improving health, has not been evaluated in any comprehensive way. We will use several existing sources of data, including specialised and national surveys, electronic primary care patient records, sales and prescriptions for NRT, and hospital admission data, that all provide different measures of smoking behaviour in England to find out how effective each of these specific policies have been. This work will help in establishing which policies are successful and effective and should be maintained, and which are ineffective and should be dropped.