How to build a biofilm

A house is made from basic components that include bricks, roof tiles and mortar. Each part is essential to allow the building to be constructed. In addition the component parts need to be assembled in the correct order, and with the correct spatial arrangement, for the house to be strong and secure. Following this analogy, biofilms are communities of microbes (where the cells can be considered the bricks and roof tiles) that are surrounded by an extracellular matrix (the mortar) that provides structure. When living in the biofilm the microbes benefit and become resistant to antibiotics and other antimicrobial agents. This can result in the formation of chronic antibiotic resistant infections. We are interested in how a biofilm is built. The main component parts that are needed have been identified and in this proposal we aim to understand how they are assembled. Understanding how they are assembled will allow the development of novel strategies to block assembly in the natural environment and therefore guide future development of novel antimicrobial compounds for chronic debilitating biofilm infections.

It is accepted across the medical and scientific community that there is an urgent need to uncover new targets to fight difficult-to-treat Gram-positive and Gram-negative chronic bacterial infections. Such infections are predominantly the result of microbial biofilms; structured complex communities of microbial cells that are enclosed in a self-produced extracellular matrix. There have been significant recent advances in our understanding of the regulatory pathways and key building blocks required for the nucleation and growth of biofilms for many species of bacteria. However it is still not understood how the extracellular and cell wall components physically interact to allow a three dimensional biofilm to develop. Bacillus subtilis is a very suitable model for biofilm formation in Gram-positive bacteria. It forms biofilms that contain differentiated cells that display a complex three-dimensional architecture. We have recently shown that a small protein called YuaB is essential for biofilm formation and that it acts in a synergistic manner with the TasA amyloid fibres and the exopolysaccharide found in the extracellular matrix to allow biofilm development. Therefore our system is ideally suited to allow us to generate a detailed understanding of how the biofilm is constructed. We aim to determine when YuaB is needed to allow biofilm formation, how the extracellular polymers interact with each other, and to elucidate the structure and function of YuaB. We will accomplish this using a collaborative interdisciplinary approach with techniques that cross the boundaries of biology and chemistry. We will utilise a combination of classical molecular genetic techniques, in association with state-of-the-art chemical and structural analyses.

A. i) Smaller Biotech companies such as Novacta, Biotica, and Aquapharm. ii) These companies have active anti-infective research programmes. They will benefit from the proposed research programme that will generate novel and exciting knowledge on a target relevant to the development of novel antibiofilm agents. iii) It is currently too early in the project to identify industrial partners specifically. The lead institution will act to protect any intellectual property and to maximise opportunities for collaborative research or licensing. The Dundee research and innovation team have a wealth of industrial contacts and close links to Scottish Enterprise, and will help maximise the impact of all findings of commercial value. As and when appropriate, results will be peer-reviewed and published. B. i) Members of the wider academic community. ii) Biofilms are responsible for the majority of chronic infections and also the majority of beneficial remediation and biocontrol processes. This work will increase our understanding of the role and mechanisms of the extracellular matrix of the biofilm thus facilitating future study and exploitation for therapeutic purposes. iii) The PDRA and PIs will attend and contribute to a variety of conferences and the PIs will present results through invited research talks, both nationally and internationally. As appropriate, results will be peer-reviewed and published. Strains and other resources will be made available as appropriate. C. i) PDRA and PIs. ii) The University of Dundee takes training of early career researchers (including PIs) very seriously, thereby ensuring a successful contribution to the knowledge-led economy of UK Plc. The appointed PDRA will be encouraged to be innovative in their work. There will be opportunities for them to train undergraduate, postgraduate and visiting scientists. They will be given multiple opportunities to present their findings at major research conferences, facilitating their career development through the acquisition and refining of key presentational and networking skills. iii) The appointed PDRA will have access to training in transferable/generic skills through the professional development schemes. In line with the Concordat 2009, the PDRA will be actively encouraged to undertake at least 5 days training in generic skills per annum. In addition, both institutes have an annual appraisal scheme to actively facilitate the career development of staff, including PDRAs and PIs. The PDRA will also be encouraged to design and supervise undergraduate projects and to become involved in science communication. D. i) The general public. ii) It is important that members of the general public are aware and supportive of how tax payers' money is spent on scientific research. Therefore as part of our work on this project, we will engage with local communities, through face-to-face discussion of our work and family focussed scientific event days. iii) The applicants are experienced, energetic and ardent science communicators. For example, the University of Dundee partners have teamed up with the Dundee Science Centre to organize a 2-day event in May 2010 entitled 'Magnificent Microbes'. This event attracted teachers, children, the general public and the local media to learn about the research going on in the Division of Molecular Microbiology and educated, inspired and entertained the public about microbiology research. Approximately 400 people visited the event and we now intend to repeat it in 2012, which would be during the course of the project.