Architecture of a biofilm

Bacteria are small single-celled organisms that cannot be seen with the naked eye. They are found in the majority of environments and exert influence on our daily lives. One reason that explains how bacteria manage this is the fact that they team-up to form social communities called "biofilms", which are the equivalent of human cities but made from bacteria. Once living in these social communities, the resident bacteria can perform a wide range of processes, and these can in turn be exploited by us, for example in sewage breakdown or in stimulating plant growth and plant protection. However, there can be negative consequences as biofilms are the cause of many chronic infections and industrial biofouling issues. The defining feature of a biofilm is that the bacteria make a "sticky glue" called the biofilm matrix that holds the cells together and protects them from changes in the environment. This protection can result in resistance to antibiotics and other cleaning agents. Given the diverse range of processes - both positive and negative - that biofilms have been associated with, it is critical that we learn how to manipulate biofilms for our own advantage. This will require understanding how the biofilm matrix is constructed and how the different components made by the bacteria to form the matrix interact. Currently very limited information is available and given the complexity of the problem, real impact can only be achieved using a multidisciplinary approach. Our research team has been assembled to combine the skills required for success. Our ultimate goal is to build and utilise artificial biofilms. Our aim is to determine the basic rules for the structure and function of biofilms that will allow for the advantageous manipulation of both natural and artificial functional bacterial communities.

Biofilms are social communities of microbial cells that underpin diverse processes that include sewage bioremediation, plant growth promotion and plant protection, chronic infections and industrial biofouling. The defining hallmark of a biofilm is that the cells are resident within a self-produced exopolymeric matrix that typically comprises lipids, proteins, extracellular DNA, and exopolysaccharides. The biofilm matrix fulfils a wide range of functions for the community, from providing structural rigidity and protection from the external environment, to controlling gene regulation and nutrient absorption. An in-depth knowledge of the biofilm matrix is critical to the development of novel strategies to control biofilm infections, or the capability to capitalise on the power of biofilm formation for industrial and biotechnological uses. To do this requires a deep understanding of the structure of the individual components, the nature of the interactions between them and their spatial-temporal organisation within the biofilm. The ultimate aim of our research is to build and subsequently utilise artificial biofilms. We propose to first determine the fundamental design principles underpinning the structure and function of biofilms, and then exploit this new knowledge for the advantageous manipulation of both natural and artificial biofilms. We have chosen the Bacillus subtilis biofilm as our model system, and propose to characterise it in exquisite detail. We will use our experimental findings to develop mathematical tools that will enable us to make predictive models; these will, in turn, inform our experimental programme in a virtuous cycle.

All health, agricultural or industrial stakeholders with interests in biofilm formation could benefit from the proposed research programme through our advances in our understanding of biofilm composition and structure, and the identification of novel biomaterials. In particular, we are pursuing the potential that at least one of the biofilm matrix components has important applications in two large industrial sectors (home and personal care). These applications are so well established that the timescale for a product to reach the market could be of the order of 2-5 years. Moreover, the organism that is the focus of this proposal, B. subtilis, is sold commercially as a biocontrol agent. Therefore the agrochemical industrial sector will also be a potential benefactor from the detail we will uncover. Further still, knowledge generated could help increase understanding of how the biofilm protects plants against pathogenic microbes. In the healthcare setting, it is well-known that biofilm formation plays an important role in antibiotic resistance and so increased knowledge may contribute to novel tractable strategies to address a problem of global imperative. These novel approaches may be attractive to Pharma industries as they offer a radical alternative to more classical drug discovery approaches. Potentially, this has huge implications for contributions to the nation's health and wealth as it may offer a significant advantage over the standard 10 year drug discovery timeline. Synthetic biology and industrial biotechnology are areas of increasing strength for the UK with strong Government support and backing via an increasing number of funding initiatives e.g. Innovation and Catapult Centres and Innovate UK calls. The findings of the proposed strategic programme will pave the way towards synthesis and manipulation of biofilms across a diversity of both known and as yet unknown uses and consequently of the creation of significant economic and social benefit.

The general public will be a beneficiary from this research over different timescales. We will keep the public informed of how their tax money has been spent on addressing the science of biofilms throughout the duration of this grant (1-5 years). The team are experienced science communicators and we have many established channels to interact with both our local and UK-wide public communities. On a longer timescale (5-10+ years) the commercial outputs of the work are expected to have a positive impact on a range of consumer products and also lead to fundamental improvements in crop productivity and solutions for antimicrobial resistance.

The proposed research will have most immediate benefit to the five multidisciplinary research groups and collaborators across three Universities over the 5 year lifetime of the programme. The PIs and PDRAs will gain from a multidisciplinary approach to addressing a scientific question which will spark novel hypotheses and increase the skill set of all involved. It is highly likely to stimulate the application of newly acquired skills to other basic research questions thus enhancing other scientific areas of UK-based research. The PDRAs will gain exposure to working in different lab environments and there will be a constant flow across the biological, physical and mathematical sciences, breaking down traditional boundaries. The PDRAs will be involved in commercial discussions in the quarterly project management meetings and through the experience gained on this project will become highly sought after in both the academic and industrial sectors. It is recognised in key growth sectors in the UK such as industrial biotechnology that there is a lack of suitably qualified individuals. Our PDRAs would be well-placed to fill this skills gap. Members of the wider academic community would likely benefit on a 3-7 year timescale when we start to publish our broad-ranging findings in journals with global impact and attend scientific conferences.