Spring 2019 Projects

Every day in the UK about 30 people severely injure their neck from being in a road traffic accident, falling, or taking part in sport. It is important that these people get the right treatment at the right time so that they make the best possible recovery. To achieve this, clinical staff need to diagnose neck injury correctly and quickly.

When someone has a neck injury an x-ray will be taken to see if the bones are broken or dislocated. Identifying the injury, however, is not easy and clinical staff can miss it or be unsure about what they see. It is thought that about 1 in 5 people with neck injuries have an incorrect or delayed diagnosis. These people can receive the wrong treatment or receive treatment too late. The potential outcome of this is that they suffer long term neck problems or, in extreme cases, paralysis or death.

Our project consists of two parts. In the first part we will test whether the program helps clinical staff make a correct diagnosis.  In the second part we would like to hear more from patients and clinicians to see how they feel about such software assisting clinicians. 

Commonly used drugs often have unwanted side effects such as being toxic to healthy cells. However, extremely small drug carriers (so called ‘nanoparticle-drugs’) have the potential to revolutionalise drug delivery. This is because they can be designed to;

i)    specifically target diseased cells
ii)    safely be transported to specific areas of the body
iii)    be ‘multi-functional’ such as delivering two synergistic drugs.
The problem is that drug carriers are often prevented from reaching their target by ‘biological barriers’, such as a capillary walls.
 
In this project we will address this by building a computer model of a common ‘biological barrier’ – a capillary wall – and investigating how nano-drugs cross it. We need a computer model because there are many factors that can affect this rate, such as the size of the carrier and the ‘leakiness’ of the capillary wall. Experimentally testing all these likely factors is unfeasibly time consuming and expensive, whereas computer models can achieve the same result for a fraction of the cost and time.

Our results will have a wide impact on the design of nanoparticle-drugs. This is a very important field as there are currently 50 ‘approved’ nanodrugs for clinical use, with many more in clinical trials for a whole range of diseases. Our computer model will help predict, at the design stage, which nano-drugs will be successful, ultimately improving the treatments of a wide variety of diseases.

Single-celled organisms such as bacteria and archaea thrive in virtually all environments around the globe, including the human body. These microbes produce extremely long hair-like appendages called flagella and pili, which project from their cell surface. Both types of filament are multifunctional and act as a means of communication between individual microbes, and between microbes and the environment. Flagella and pili also enable microbes to swim, attach to and “walk” along surfaces, exchange genetic material and form biofilms. Examples include dental plaque or dangerous contamination on hospital catheters and implants.

In beneficial microbes, such as those resident in the human gut, proper functioning flagella and pili ensure diversity and fitness of the microbiome, which is crucial to our digestion, immune system and the prevention of immune deficiency, autoimmune disease, allergies, diabetes and obesity. On the other hand, in infectious disease, pili and flagella enable infection and spread of nonbeneficial or even pathogenic bacteria, as well as antibiotic resistance.

We propose to investigate the dynamic function of microbial filaments at so far unprecedented detail by combining state-of-the-art bioimaging techniques with cutting-edge computer simulations. The knowledge will help design new drugs to fight infectious disease and support a healthy microbiome.

This project focuses on the broad area of dementia prevention. It will be embedded within our portfolio of research which examines how lifestyle approaches, such as exercise, diet and behaviour, can affect a person’s risk of developing dementia. The evidence clearly shows that physical exercise is one of the best ways to reduce this risk, but the challenge is to change people’s behaviour and get them exercising more. Our online research platform, PROTECT (www.protectstudy.org.uk) is tailor-made to support this type of research.

Based on the strongest evidence available, we have developed a digital exercise programme, Train for the Brain. It will launch shortly, and collect a rich dataset from 4500 adults over 50. Data will include measures of physical fitness and brain health (such as memory, reasoning, attention). A critical question is how these aspects of health correlate with each other, and how they could be used to tailor physical activity programmes to an individual.

This project will involve detailed analysis of this large, unique dataset to answer these questions. It will enable us to optimise the exercise programme which, if effective, could be the first affordable dementia prevention programme in the UK.

Communication between cells is essential for the regulation of the development and maintenance of all multicellular organisms. Signalling molecules play a pivotal role in this communication and are responsible, for example, for establishing the proper location of organs embryonic development.

In addition to their role during development, these signalling molecules also regulate the wound healing process. In particular, they recruit appropriate cells to the wound site and encourage them to replicate to repair the tissue. One might then naively think that increasing the prevalence of these molecules would then be an excellent strategy to improve and hasten wound healing. However, increases in the rate of cell replication also increase the likelihood of cancerous tumours forming, and so a careful balance is required.

A thorough understanding of the quantitative nature of distributions of signalling molecules in a biologically realistic setting is currently lacking. We aim to address this to pave the way for the development of improved wound and fracture treatment. To achieve this goal, we will combine biophysical and mathematical approaches to examine how the distribution of signalling molecules changes over time, and how this ultimately dictates the development and growth of the biological tissue.

Fungi infect millions of people every year. Although most of these infections are minor and easily treated, millions of these infections are life-threatening. In fact, it has been estimated that fungal infections kill about 1.5 million people worldwide each year. That's at least as many people killed by tuberculosis or malaria. These life-threatening infections target people with poor immune systems such as those that have had serious medical conditions, like HIV/AIDS, or intensive medical treatments that reduce the immune system. This means that fungal infections pose a serious risk to human health.

To make matters worse, there are several problems with treating fungal infections. The development of drug resistance means some treatments don’t work and many people with serious infections can die. There is an urgent need to produce new drug treatments to stop fungal infections.

This project will use make new computer software to find targets for new drug treatments. These new treatments will make use of multiple drugs in what is called combinational therapy. In the future these new targets and new therapies could help treat fungal infections and lower the high death rate associated with these infections.