Autumn 2017 Projects

Amyotrophic Lateral Sclerosis (ALS) is a devastating disease, which develops as muscle paralysis and eventually the patient dies due to breathing problems. ALS is caused by loss of motor nerves or neurons, which carry signals from the brain to the spinal cord and from the spinal cord to the muscles. Since motor neurons are very important, loss of these neurons eventually leads to paralysis and death. However, the ways by which these motor neurons are lost are poorly understood. Understanding how motor neurons die is important in making treatments that can stop or even reverse the motor neuron death.

We have developed a “disease-in-a-dish” model of ALS by using spinal motor neurons taken from ALS patients that show signs of the disease such as increased risk to stress and shape defects.  To understand how motor neurons die, we will look at how genes work in 800 single neurons from ALS patients and healthy people. Inside a cell, genes work together to allow the cell to function normally. Our analysis will investigate our these genes work together and what goes wrong with gene-gene communication in ALS. By doing this we hope to find the cause of motor neuron loss. Once we find the genes that possibly cause motor neuron loss, we will test these genes in human neurons as well as in fish brains. Fish and humans share the same basic body plan and share many genes with humans. Additionally, given the ease of handling and testing the fish, it’s an attractive system to understand ALS. We hope that identifying genes causing motor neuron loss will pave the way for making drugs that increase motor neuron survival in ALS.

Many people have wounds that are slow to heal. Wound healing is an increasing challenge with age and in common medical conditions such as diabetes. One recent idea is to apply electric fields to wounds to make them heal quicker. However, no one knows how this works.

Studying this in the human body is too complicated. Instead we will use a simple organism that moves in a similar way to human cells. This organism is found in the soil all around us. We will take this organism and artificially apply electric fields to see how it moves.

Our ultimate aim is to design personalised point-of-care devices that can be applied to wounds to speed up their healing.

Ragweed is a North American plant species that has rapidly spread throughout Europe over the lastfew decades. It causes an allergic reaction for many people each year as they come into contact with its pollen and is associated with an economic cost of billions of Euros each year. It is just one example of an invasive species that causes health problems. As humans increasingly move animals and plants around the globe and climate change causes species to colonise new areas, invasive species are likely to cause an increasing number of problems for health. For example, the Asian Tiger Mosquito is becoming established in Europe. It transmits yellow fever, chikungunya fever and more than eighteen other diseases to humans. Such species can arrive unexpectedly and action must often be taken rapidly to prevent their spread. In order to control invasive species and limit their effects on human health, we need to understand how they arrive, establish and spread through the landscape.  We use ragweed as a case study to improve our understanding of a key question: how plants and animals colonise new areas during invasions and climate change.

Invasions are studied on several levels, ranging from models describing population expansions conceptually to highly complex mathematical models focusing on predicting the expansion of a species in a specific area. The latter require a large amount of information on the biology and the types of vegetation and land use in the region. However, as more and more species arrive we will not have time to collect detailed data before action needs to be taken.

Our research aims to find out how simple and generic we can make models of plant and animal invasions and whether we can use these more generic models to predict sudden invasions of harmful species.

Being physically active has been shown to have a beneficial effect for people with depression, by improving mood and minimising the symptoms of depression. Despite this, we do not know whether intensity of physical activity is important, nor how long the effects of different intensities last in populations with elevated depressive symptoms. This project aims to address these knowledge gaps by measuring the physical activity of people with depression / low mood over the course of a week. During this time we have also asked people to report their mood at different points of the day, so that we can measure the amount of activity being done around the time of the mood score. The impact of this research will allow a better understanding of what intensity of physical activity may be related to depression, which will allow us to further examine how physical activity might be used to treat depression and low mood, as an alternative or as an addition to medication. The results also have the potential to benefit not just those in a clinical population, but also for those in the ‘healthy population’ who sometimes experience low mood.

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. One group of signalling proteins are the members of the Wnt signalling family. Wnt proteins are responsible, for example, for establishing the brain primordia during embryonic development or the maintenance of tiny villi in the wall of the small intestine.

In addition, these Wnt 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 a good strategy to improve regeneration and hasten wound healing. However, increases in the rate of cell replication also increase the likelihood of cancerous tumours forming. Indeed, in 90% of patients with intestinal tumours the Wnt signalling pathway is hyperactive. And so, a careful balance is required.

A thorough understanding of the quantitative nature of distributions of Wnt signalling molecules in a biologically realistic setting is currently lacking. It is our aim to address this challenge by a combination of wet lab experiments and mathematical modelling. Our simulation will enable us to predict the distribution of Wnt molecules in a growing tissue such as a developing embryo, a growing tumour or a healing wound. A deeper understanding of Wnt distribution will pave the way for the development of improved wound and fracture treatment. To achieve this goal, we will combine biological 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.

This project will develop new ways of studying individual microbial cells. Being able to do this is crucial as there are no two identical cells in a population of cells with the same genetic make-up. On the contrary, some cells will behave very differently from most of the others.  For example, some of the bacteria commonly found in our intestines grow much more slowly than others.  Even more surprisingly, a small number of these cells can survive after being given antibiotic doses that would usually kill them. These cells that can survive antibiotics are a serious threat to human health. They are responsible for persistent infections in people with weakened immune systems. So it is crucial to be able to understand these cell differences in taking up antibiotics and surviving drug treatment.

We aim to develop experiments that will allow us to study these rare cells that can survive antibiotics. We then hope to suggest guidelines to develop new antibiotic drugs. There are usually less than 0.1% of these rare cells. This means we will have to study tens of thousands of them to learn about them. In order to study how these cells respond to drug exposure we need to keep track of each individual cell for one or more days. We will do this by using microscopy to get images of each individual cell. We will also use microfluidics to hold each individual cell in place while changing the environment around it. For example, we will introduce nutrients to mimic the cell natural environment or antibiotic drugs for drug treatment. We will fully automate these experiments. This will reduce the demand for user input. We will also develop software that will analyse the images that we get. This will give us information about each individual cell at the different stages of the experiment. This will include cell length, width and growth. 

In addition, we will use bacteria that produce a fluorescence protein every time a specific gene is expressed. This fluorescence will change over time. This will let us measure how the expression of different genes changes over time. At the end of each experiment we will gather several pieces of information for several thousands of bacteria. We will use this information to develop a mathematical model. This model will let us predict the fate of single bacteria under antibiotic treatment. It will also tell us the best drug dose to use.

This project will give us information that will help in combating bacterial infections. It will be of particular use in people with weakened immune systems such as children, the elderly or people affected by cystic fibrosis or HIV. The technology we will develop will make it easier to test antibiotics. It will also help to design new and more effective drugs. Therefore, this will be relevant to pharmaceutical companies and organisations developing antibiotic drugs.