Designing of novel biosensors using synthetic biology approaches

Infectious diseases are still a major cause of death, disability and social and economic upheaval accounting for more than 11.9 million deaths a year worldwide. Current efforts concentrate on the development of novel antimicrobial and therapeutic strategies. However, early interventions based on state-of-the-art diagnostic strategies and novel treatments that will accelerate the detection and management of bacterial infections is paramount to substantially reduce the impact of infectious diseases. Many bacterial pathogens produce signature signal molecules to control their virulence by a process known as quorum sensing (QS). Our laboratory has years of expertise studying these signalling processes and in designing biosensors for their detection. However, these biosensors are usually not sensitive enough to detect the very low levels of these molecules in human samples, especially during the early stages of infection. We have recently been using synthetic biology strategies with the aid of molecular biology and computational modelling approaches to design sophisticated synthetic circuits which can sense with increased sensibility the signature molecules and amplify the responses to low signal levels. These strategies are leading to many applications, some of which will have clinical outcomes. The aim of this project is to recycle some of these engineered circuits for the design of highly sensitive biosensors which can be used to detect early stages of infection through the detection of QS molecules and trigger a genetically-controlled biological response which will additionally result in a reactive first line of defence against the invading pathogen. The project will provide extensive training in molecular biology, synthetic biology, computer modelling, microscopy and analytical biochemistry techniques.

The University of Nottingham is one of the world’s most respected research-intensive universities, ranked 8th in the UK for research power (REF 2014). Students studying in the School of Life Sciences will have the opportunity to thrive in a vibrant, multidisciplinary environment, with expert supervision from leaders in their field, state-of-the-art facilities and strong links with industry. Students are closely monitored in terms of their personal and professional progression throughout their study period and are assigned academic mentors in addition to their supervisory team. The School provides structured training as a fundamental part of postgraduate personal development and our training programme enables students to develop skills across the four domains of the Vitae Researcher Development Framework (RDF). During their studies, students will also have the opportunity to attend and present at conferences around the world. The School puts strong emphasis on the promotion of postgraduate research with a 2-day annual PhD research symposium attended by all students, plus academic staff and invited speakers.