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Escherichia coli (E. coli) has multiple acid resistance systems which protect the cells against low pH. One of these systems is AR2, which requires the presence of amino acid glutamate in the growth media. AR2 can be activated by exposing exponential phase cells to a pH of 5.5 for 30-60 mins. Cells respond to this induction by showing increased levels of survival upon exposure to pH levels of 2.5 and below. In our study we are comparing the survival of different E. coli species such as commonly used K-12 lab strains- BW25113 and MG1655, the pathogenic strain O157:H7 and a probiotic strain Nissle 1917, when exposed to extreme acid stress at pH 2.5 with and without their AR2 system being induced at different growth stages such as exponential, late-exponential, and stationary phase. Furthermore, we are examining how the bacterial signalling molecule indole can inhibit the induction of AR2 system by either directly or indirectly binding to EvgAS, one of the two component systems involved in induction of AR2 system.
Computer simulations have become essential tools to help understand, and even to predict, the results of chemistry experiments. Many fundamental processes require the quantum mechanical nature of molecules to be taken into account for a realistic simulation. At present, however, we are unable to treat correctly the dynamics of more than a few atoms using quantum mechanics. As a result, one has to simulate either a reduced model system exactly, or the full system using approximate methods such as classical molecular dynamics. A useful route to overcome the limitations is to treat part of a system using quantum mechanics, and part of the system using more approximate methods. The proposed research aims to develop a promising new mixed dynamics algorithm in which the all important, but theoretically difficult, interaction between the different parts of the system is treated rigorously.As a test of the method we propose to simulate experiments that scatter water molecules off the surface of a protein. The scattering process will be described using full quantum mechanics, while the protein environment will be described dynamically and explicitely, but more approximately. Results should give insights into the nature of solvation at the molecular level.
Modelling and design of new interferometers for precision metrology with either passive or active suppression of the impact from spatial laser beam distortions, to support the design of new ground-based gravitational wave detectors such as the Einstein Telescope and LIGO upgrades'
Antibiotics underpin modern medical, veterinary and farming practices worldwide. However, the efficacy of antibiotics is decreasing. A simple genetic system called mar, which can provide protection against multiple antibiotics, will be the focus of our project. Briefly, mutations in this system result in triggering of bacterial defences. Consequently, the bacterial cell is able to protect itself from many different toxic agents. We seek to identify and understand all of the cellular pathways that link this defence system to antibiotic resistance. By understanding pathways to drug resistance, we will provide new opportunities to control bacterial infections. Importantly, the pathways we will investigate are similar in many microbes. As a result, our findings will be applicable to many bacterial infections and so of broad interest. Antibiotics are often used with no knowledge of the infecting microorganism. Hence, widespread use of antibiotics favours the emergence of antibiotic resistant bacteria. Our experiments will be done using a bacterium called E. coli. This organism is commonly found in people and animals, including pigs. Furthermore, pigs are among the most common recipients of antibiotics in the EU and the number of serious E. coli infections in people is increasing. Indeed, the type of E. coli we will investigate has acquired mutations in the defence system we will study. Therefore, we will address a major health issue relevant to the UK animal food production industry as well as animal and human health. Importantly, this application comes at a time when there are global calls for a better understanding of antibiotic resistance.