MRC Centre for Molecular Bacteriology and Infection

Bacterial infections continue to cause immense human suffering and mortality throughout the world. We lack good vaccines for many bacterial diseases and the unabated, alarming worldwide rise in antibiotic-resistant bacterial pathogens has led to many high level international calls for action. It is widely appreciated that new ways to tackle bacterial infections will benefit from better understanding of the infectious processes and associated immune responses. Surprisingly, despite the importance of this problem, the MRC Centre for Molecular Bacteriology and Infection (CMBI) at Imperial College London is the only research Centre of excellence focussing exclusively on bacterial infection research (either in the UK or overseas). Furthermore, there is considerable concern about the shortage of UK-trained academics and clinicians developing research careers in bacterial infection biology. Over the last few years, with Imperial College and MRC support, the CMBI has developed into a major focal point for research and training in this area. Over the next five years we aim to refocus our training programme and strengthen research themes in the areas of bacterial physiology and pathogenesis, AMR, host immunity and the microbiota - bacterial communities that naturally inhabit our bodies and which have crucial but poorly understood roles in their interactions with pathogens, the emergence of antibiotic resistance and in host immune function.

Underpinning these research themes will be a special emphasis on single cell analysis. Traditional bacteriology research involves studying bacteria as populations - either during growth in laboratory media or during infection. However, it is clear that even though these populations can be genetically identical, individual bacterial cells within them behave differently, and this variability has very significant implications for the outcome of infections and the development of antibiotic resistance. Recently, the large-scale study of individual cells in a population - single cell analysis - has become more feasible through the development of new specialist techniques and equipment. To support and enhance this research in the CMBI we require a suite of dedicated equipment for use in an environment where human pathogens can be handled safely. Therefore, we are proposing to establish a high throughput single cell analysis facility.

Together, our new objectives are to (1) create new research teams focussing on AMR and the microbiota; (2) maintain a strong focus on mechanistic understanding of processes governing bacterial physiology, pathogenesis and host immunity; (3) establish a high-throughput single cell analysis facility; (4) build strong local, national and international collaborations with academic and clinical colleagues outside the Centre who work on other aspects of bacterial disease, and with whom we can share expertise; (5) extend our highly successful PhD programme - which contributes to the national effort to train the future generation of researchers both academically and clinically; (6) exploit a clear partnering strategy so that our discoveries can be translated into practical benefit in areas such as diagnostics, antibacterials and vaccines.

Imperial College will provide three new academic posts to expand research capacity (two Lectureships and one Senior Lectureship). Two posts are to study complementary aspects of AMR and one post will be used to appoint a specialist on the microbiota.

An underlying theme of the Centre is the study of bacteria at the single cell level. Most bacteriology research involves studying bacteria as populations - either during growth on lab media or during infection studies. However, it is clear that even though these populations can be genetically identical, individual bacterial cells within them behave differently, and this variability has very significant implications for the outcome of infections and the development of antibiotic resistance. To accelerate work at this level, we wish to establish a high throughput single cell analysis (HTSCA) facility, which will comprise an existing, MRC-funded BD Aria III cell sorter, a BD FACSCalibur analyser, and new equipment that we request from the MRC, comprising a Zeiss Z1 microscope, CellASIC ONIX2 microfluidic system and LionheartTM FX Automated Live Cell Imager. We also request funding from the MRC for a facility manager to maintain, train and help CMBI users with experiments and data analysis.

A major component of this proposal is a continuation of our successful PhD training programme. This will consist of 16 studentships, of which 12 (nine MRC and three Imperial contributions) will be non-clinical three and a half year studentships and four will be clinical research training fellowships (three MRC and one Imperial contributions). We also request support for our Centre manager and a small budget for other Centre activities.

Academics and clinicians: The academic and clinical sectors will continue to be the main beneficiaries of the CMBI: Firstly, the training programmes of the CMBI will produce a cohort of research scientists and scientifically trained clinicians who might develop their careers as infection biologists or move into different research fields. Secondly, the research themes in the CMBI will generate new theoretical and practical knowledge relevant to bacterial infection biology, and new resources (reagents, bacterial strains, experimental procedures etc.) that will benefit researchers in the immediate and wider field. Beneficiaries will be the large international research community that works on pathogenic bacteria, who will read papers published by CMBI researchers that could influence future research. Since some of the resources will be relevant to fundamental bacterial processes, beneficiaries will also include bacteriologists working on non-pathogenic bacteria. Clinical infectious disease specialists, structural biologists, immunologists, cell biologists, geneticists, vaccinologists and systems biologists will also be beneficiaries.

Industry: The industrial sector will be a long-term beneficiary of the CMBI. The existing and new research themes in the CMBI will generate knowledge that could inform new product development relevant to managing bacterial infections, and consequently stimulate development of appropriate delivery systems by the biomedical engineering sector. We will exploit Imperial Innovations and industrial partners to translate work for broader benefit.

Society at large: Benefits to society at large will be twofold: In the short term, the CMBI will provide employment for several individuals at the postdoctoral level, thereby directly contribute to the national economy. Some of our trainees are likely, through subsequent employment, to benefit the UK healthcare system, biotechnology and pharmaceutical industries, as well as the academic base in the UK and abroad. The research will improve our understanding of diseases caused by bacteria. Furthermore, the management of diseases caused by pathogenic bacteria has a costly impact on public health budgets. Outcome of research conducted in the CMBI could potentially inform novel interventions and strategies to manage infections caused by pathogenic bacteria, and ultimately contribute to improved public health, wellbeing and quality of life. Where appropriate, results will be communicated to the wider public via more readily accessible publications, e.g. through the media and popular science publications. To maximize the impact of these endeavors, we will seek advice from the Imperial College (IC) Communications Division, which incorporates Media Relations and Research Communications teams. Centre researchers will continue to engage actively with local and non-local primary and secondary schools/6th form colleges, both through school visits and inviting students to outreach events (National Science and Engineering Week [2014], Imperial Festival [2015, 2016]), where we communicate facts about beneficial and pathogenic bacteria, antibiotic use and AMR, vaccination etc. CMBI postdocs will organise and host an Imperial Fringe event on 'Bacteria and AMR' in 2017 and continue with this or a different theme in subsequent years. Following on from the success of the Imperial Festival in 2015 and 2016, at which the CMBI was part of the Superbug Zone with other research groups working as part of the Antimicrobial Research Collaborative (ARC), our postdocs are already planning for the next year's Festival in May 2017.