Clostridioides difficile is the most common cause of hospital-acquired life-threatening infections and the incidence has escalated in recent years due to the high number of patients on broad-spectrum antibiotic therapy. While antibiotic treatment is effective, ~28% of the patients suffer from relapse. C. difficile is also becoming resistant to many of the antibiotics, and alternatives to antibiotic treatment are urgently required. One such strategy, is the use of faecal therapy where gut microbes from a healthy donor is given to patients to reconstitute a healthy gut microbiome that can resist proliferation of C. difficile. Recent studies of faecal therapy suggest a greater than 90% success rate, particularly in those patients suffering from chronic relapse. However, faecal therapy is aesthetically unappealing to patients and the healthcare workers, and there are also potential risks of transferring unknown pathogens from the donor to the patient. The aim of this project is to develop a cocktail of bacteriophages or bacterial metabolites that can be formulated as a defined treatment to give a safer, more appealing alternative to faecal transplantation. Such cocktails will be designed to modulate the gut microbiome which result in protection against C. difficile infections. The effective designed formulations will then be optimised with the objective of developing human trials in the future.

It is a common occurrence in mathematics that in order to understand a given thing, we add extra structure to it - seemingly making it more complicated, but in fact making it easier to obtain insight on it. An analogy would be ordering things in the real world. The thought of all possible words in a language seems quite overwhelming, but ordering them lexicographically and writing them in a dictionary, we have an easy way to obtain information about any given one, despite seemingly having complicated things by imposing extra structure (knowing when a word comes before another). In mathematical terms, we have turned words into a category. Categories are commonly studied through their representations, meaning actions on things that are more easily accessible, not unlike books written in a certain language: Not all of the language will be visible in a given book, but the more books we read, the better we know the language. For certain important categories called algebras, there is a very well-developed theory of such representations. In recent years, it has been found that in order to study questions about categories, it is often useful to add even more structure to obtain 2-categories, e.g. the "category of all categories". The study of examples of representations of such 2-categories has led to some exciting breakthroughs on long-standing problems in pure mathematics. Our project is to extend the theory of representations of algebras to representations of 2-categories with analogous properties to those of algebras, with the goal of providing a structured framework for the examples that have been observed, hence facilitating future use of these successful concepts.

Pathogens use a suite of effector proteins that target host proteins to subdue immune systems and enable infection of the host. Occasionally, a pathogen strain evolves to infect a new host - a process known as a "host jump". Host jumps exert a strong selection pressure on the effectors to adapt to their new host environment, ultimately leading to effector and pathogen specialization. This project investigates pathogen adaptation and effector specialization after a host jump in the rice blast fungus, a complex pathogen of grasses. The rice blast fungus is critical for global food security as the main destroyer of the rice crop. It secretes a multitude of effectors. Avr-Pik is one such effector that targets rice proteins containing heavy metal associated (HMA) domains to enhance virulence. However, rice uses HMAs as sensors integrated in an immune receptor that detects Avr-Pik to mount defence. Recently, the crystal structure of a complex between Avr-Pik and the HMA from the immune receptor Pikp has been determined in our Laboratories. We showed that the affinity between Avr-Pik and HMA determined the sensitivity of the immune receptor. This offers an unprecedented opportunity to study the effect of natural variations on affinity between Avr-Piks and HMAs at the biochemical level. This project aims to exploit natural variation in effector and host proteins to fine-tune the sensor in Pikp to recognize a broader range of blast fungi.

Estuaries are more than simply areas of mud and marsh that represent the transition zone between rivers and the ocean. They play a vital role in our economy as sites of leisure and commercial activities, such as fishing and boating. In addition, they are important nursery grounds for many species of economically important fish that later migrate to the open sea. As approximately 40% of the world's population live within 100 km of the coast, estuaries are also some of the most vulnerable sites for impact from man's activities. Not only can they suffer from activities occurring within the estuary itself, but they also mark the point where pollutants gathered by rivers from large areas of the interior can accumulate. One of the major pollution concerns in estuaries arises from the excess river borne concentrations of phosphate and nitrate. These can be derived from a variety of sources, such as run off from fertilised fields and discharge (accidental or purposeful) from sewage treatment plants. Regardless of their source, they can cause severe problems, such as stimulating the growth of excess algal growth that can deplete the water in oxygen and causing widespread fish kills, or causing the growth of poisonous algal species (red tides) that cause shell fish fisheries to be closed. Although this problem has been recognised for some time, and monitoring activities by bodies such as the Environment Agency and water companies play an important role in keeping pollution in check, there are still major gaps in our knowledge. In particular, it is apparent that a large proportion of the flux of nitrate and phosphate are delivered to estuaries by sudden storm events, but most monitoring takes place at fixed times that are spaced too far apart to capture these events. This is a major gap in our knowledge that will become more important as the intensity and frequency of storms are likely to increase due to climate change. Additionally, the phosphate and nitrate load of rivers can take many forms - dissolved and particulate, organic and inorganic - and relatively little is known about the concentrations of these different forms varies throughout the seasons and during storm events. Only if we are able to fully understand these processes will we be able to take the necessary steps to identify and control polluting sources of nitrate and phosphate to estuaries. Our research seeks to address this gap in our knowledge by carrying out detailed monitoring of the many forms of phosphate and nitrate that enter Christchurch Harbour estuary (Dorset) from both the rivers and the sea over the course of a year. We will be using state-of-the-art technology (much of it developed by ourselves) that will allow us to monitor they key parameters at intervals of every 30 minutes. Hence, we will be able to capture the effects of sudden and short-lived storms that have eluded previous studies and routine monitoring practices. We will then use the results of our study to examine how these sudden storm events affect the distribution of phosphate and nitrate within the estuary. In particular, we will examine what happens when sediments are stirred up in the estuary by storms - do they remove or add phosphate and nitrate to the system? We will also examine the effects of these sudden storms on the biological activity in the estuary. Again, do they increase or decrease the growth of algae, and what difference is there if the storm happens in the summer or the winter? The various threads of our study will be drawn together into a powerful statistical model that will allow us to better understand the transfer of phosphate and nitrate from rivers, through estuaries and into the coastal seas, and the role that storms play in this process. Our results will then allow policy makers to make more informed decisions about how we can seek to reduce pollution of estuaries by nitrate and phosphate.