Microbial Research on the Norwich Research Park
Although they are microscopically small, microbes are vital to us in many ways. For the purpose of these pages, the term "microbe" encompasses bacteria, yeast and other fungi and viruses. Microbes play many roles in the earth's environment from recycling dead plant and animal matter through the soil, removing carbon dioxide form the atmosphere by photosynthesis in the oceans and "fixing" nitrogen from the atmosphere to form nitrogenous fertilizer for plants. Some microbes can make humans very ill whilst others can help in maintaining our health. Likewise plants suffer from diseases caused by microbes but other microbes can be very beneficial to them, for instance in assisting them to absorb nutrients such as phosphate. Microbes can also be grown in cultures to provide us with a wide range of drugs and antibiotics, are used in the manufacture of food and drink and even biofuels.
Over 40 research groups on the NRP focus on understanding the basic genetics, physiology and metabolism of microbes. This research is leading to exciting discoveries with potential applications in the pharmaceutical, agricultural, food processing and environmental monitoring/remediation industries.
Microbes in Norwich is an NRP-wide initiative aimed at drawing together the research effort on the park through regular meetings and providing a "one-stop-shop" of the key researchers on the NRP and their research interests. These pages are not intended to give a comprehensive overview of all the microbial research on the NRP; rather being aimed at giving a flavour of the kind of work underway.
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Fundamentals of the Control of Bacterial Metabolism and Growth
Microbe-Plant Interactions and the Global Nitrogen Cycle
Understanding Microbial Diseases of Plants
Human Diseases Caused by Microbes
Improving Food Safety from Microbial Contamination
Using Microbes to Improve Health
Industrial Uses of Microbes
Fundamentals of the Control of Bacterial Metabolism and Growth
A significant amount of the microbial research on the NRP is aimed at understanding how microbes gain energy and nutrients, as well as sensing and communicating with their environment. In particular work in the School of Biological Sciences at UEA and Molecular Microbiology at JIC. Essential processes such as respiration and nutrient uptake are being analysed to work out the role of specific proteins and other molecules inside the bacterial cell that are crucial for these processes. As well as investigating the biological systems within microbial cells, NRP scientists are also learning more about how these cells signal to each other. Understanding the mechanisms responsible for generating, detecting and interpreting the signals sent between microbes is a rapidly expanding area of interest with considerable expertise on the NRP.
More information on how bacteria respond to their environment
Some bacteria have relatively complex life cycles with a large number of signalling systems which allow them to respond changes in the local environmental conditions. The Streptomycetes are an important example since they produce a large number of useful antibiotics at certain stages of the life cycle. A number of researchers within the NRP are working to understand the genes that control the life cycle and antibiotic production.
More information on Streptomyces growth and antibiotics and on signalling pathways
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Microbe-Plant Interactions and the Global Nitrogen Cycle
Possibly the most well-known of such interactions is the relationship between legume plants (such as peas, beans, and clover) and bacteria that live in tiny nodules on the roots. These bacteria have unique metabolism that enables them to "fix" nitrogen gas from the atmosphere, and convert it into a form that the plant can absorb. This relationship has underpinned crop rotation systems to promote soil fertility for centuries, and understanding how it operates at a genetic and biochemical level is a focus of almost 80 researchers on the NRP. The industrial method for fixing nitrogen is energetically very expensive and leads to large emissions of carbon dioxide, contributing to the problems of global warming. When considering all of the components of the food chain from farm to supermarket shelf, the use of man-made nitrogen fertilizer has the greatest impact on greenhouse gas emissions. Soil bacteria are also involved in other aspects of nitrogen metabolism so a full understanding the natural nitrogen cycle is important to minimizing our impact on the environment.
Genes involved in the whole biochemical process of nitrogen fixation have been identified in the bacteria concerned, and the structures, functions and interactions of some of the proteins involved are now being analysed. The other important aspect is the signalling system by which the bacteria and legume plant can recognise each other. We have a good understanding of the microbial side of the signalling partnership but recent studies of mutants in the legume species Medicago truncatula are allowing us to identify genes involved on the plant side.
One of the ultimate, though still distant, goals of such research is to develop an agriculturally important crop, such as wheat, that can host these nitrogen-fixing bacteria, and hence reduce the levels of fertiliser needed for high crop yields.
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Understanding Microbial Diseases of Plants
Plant diseases are responsible for devastating crop losses worldwide, and one of the world's largest concentrations of expertise in this subject is based at the NRP. Much of the research is aimed at understanding the response of plants to microbial infections and is described in the Plant section. However, significant effort is placed on understanding the genetics and evolution of some of the microbes themselves.
Human Diseases Caused by Microbes
Excluding food-borne diseases (see below), research programmes are underway across the NRP to tackle a number of microbial diseases affecting humans. These include Pseudomonas aeruginosa (infecting burns, wounds, medical implants and the lungs of cystic fibrosis patients), Bordetella pertussis (causes whooping cough), Streptococcus pneumoniae (pneumonia), water-borne gasteroenteric diseases (such as Cryptosporidium), tuberculosis-causing mycobacteria and MRSA, the so-called "super-bug". There is also significant research into the trypanosome diseases sleeping sickness and Chagas heart disease. Although microscopically small, trypanosomes are protozoans and not microbes as we defined them at start of the microbes pages.
Identifying possible targets for novel drug development
As disease-causing microbes develop resistance to existing drugs, the pressure is on to develop new anti-microbial drugs. Understanding more about the biological processes necessary for bacterial survival and multiplication will give clues as to the possible targets for new drug molecules. The mechanisms responsible for cell recognition, adhesion to host cells, iron uptake, and DNA replication in a number of bacteria are all under investigation by NRP scientists with the aim of understanding the role and importance of these processes in microbial infection and host interaction. Ultimately this knowledge may lead to the development of specific drugs to disrupt these processes and kill harmful microbes.
More on microbial drug targets
More on novel anti-microbials
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Improving Food Safety from Microbial Contamination
Some food we eat may contain bacteria that can cause illness and even death. These are killed by proper cooking but contamination can still occur if food is not properly handled.
The Institute of Food Research is studying bacteria such as Salmonella, Campylobacter, Clostridium botulinum (responsible for botulism), and E. coli, with the aim of helping the food industry make our food safer for longer.
Understanding the conditions in which these harmful bacteria thrive is crucial to eradicating them from the food chain, so research is aimed at modelling and predicting the growth of bacteria in food, as well as identifying features of the bacteria which enable them to infect us.
Close-up analysis of the surfaces of E. coli and Salmonella using scanning probe microscopy has revealed detailed information about the surface of some food pathogens, giving insights into how the bacteria swim and attach themselves to cells prior to infection.
The complete genome sequences of several food-borne bacteria are now available, enabling scientists to monitor the activity of specific genes in these harmful microbes. Scientists at the IFR are analysing gene activity prior to and during infection, as well as under different environmental conditions. Pinpointing the specific genes that are involved in the infection process has been possible thanks to the microarray facility at IFR. Understanding how these genes function will help in methods to control and monitor them.
Listeria bacteria can be found in milk products but whilst one type is harmful, and there are several harmless forms. Scientists at the Institute of Food Research (IFR) have recently completed an EU-funded project to exploit the infection capability of the harmful form of the bacteria. Their findings have been used to develop a simple test (ELISA) using antibodies raised to some of the proteins involved in infection. Prototypes have been prepared for the diagnostic test in both microplate and dipstick formats, but further development funding is needed before the new tests can be fully evaluated.
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Using Microbes to Improve Health
There are numerous ways in which the activity of microbes can be harnessed for the benefit of human or veterinary health. Below is a selection of examples.
i) Streptomyces coelicolor
Streptomycetes are bacteria that naturally live in the soil. The Streptomycetes are used to produce the majority of antibiotics used to treat human and veterinary diseases. They have a unique life cycle that is being studied by scientists at JIC, with the goal of understanding more about bacterial physiology and development in general. The complete DNA sequencing of the Streptomyces coelicolor genome, achieved through collaboration between JIC and the Sanger Centre in Cambridge, UK, is now underpinning a new initiative coordinated by the JIC, using a combination of proteomics and mutations to investigate the function of the 8,000 genes in the bacterium.
The JIC scientists are focussing on three clusters of genes responsible for the production of three different antibiotics by the bacterium. The genome sequence information has revealed a possible 18 more gene clusters that may also participate in antibiotic manufacture. It should now be possible to develop completely novel and valuable chemicals to use as pharmaceuticals or in agriculture.
Work at UEA is aimed at using molecules produced by some Streptomyces species as the basis for novel pharmaceuticals with potential uses as anti-cancer agents or immuno-suppressants.
ii) Probiotics and competitive exclusion
The gastrointestinal tracts of humans and animals harbour large and complex populations of micro-organisms that play a vital role in the maintenance of health. The market for "probiotics" is expanding, based on the premise that "beneficial" bacteria delivered to the human or animal gut will out-compete any harmful bacteria that may be there, as well as possibly delivering their own health benefits. The Institute of Food Research has played a significant role in investigating the interactions between the various species of "friendly" bacteria known as commensals and with the human body.
iii) Lactic acid bacteria as delivery vehicles for vaccines
Administering vaccines and other therapeutics and ensuring that they reach their target can be difficult. However lactic acid bacteria (LAB) can be exploited to manufacture and deliver vaccines and other biologically useful material to the gut. Here, they stimulate immunity that is protective at the site of pathogen entry, namely the lining of the gut. LAB-based vaccines are easy to administer, survive in stomach acid and are economically attractive in that they synthesize the therapeutic agent themselves.
iv) Harnessing microbes for drug delivery
Some bacteria make molecules that could potentially be harnessed for use in the pharmaceutical industry. Toxins from bacteria such as cholera, for example, pass easily through the skin, making a deactivated form of this toxin a potential vehicle to administer drugs without using needles to vaccinate the patient. This system is being developed by scientists at the School of Chemical Sciences and Pharmacy at UEA, with a view to being able to deliver vaccines against cancer.
v) Production of fully folded proteins by bacteria
An important breakthrough made by scientists on the NRP on the mechanism of export of completely folded proteins across bacterial membranes by the "Tat" machinery has implications for understanding how bacteria cause infections. It also has potential for use in the production of functional proteins in, for instance, Streptomyces cultures since exported proteins are very much easier to recover from the culture medium.
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Industrial Uses of Microbes
i) Microbial biosensors and soil remediation
Scientists at UEA are investigating methods for using microbes as monitors of environmental pollution. Specific proteins isolated from microbes change according to the environmental conditions; these have been harnessed to detect changes in, for example, nitrate content of water to monitor excessive discharges into waterways. There is also research into the use of soil microbes to remove contaminants, such as organophosphate pesticides and heavy metals from soils.
ii) Yeasts for the food and drink industry
Yeasts are well known for their uses in making bread, beer and wine. Over the centuries, many strains have been developed for specific purposes. The UK National Collection of Yeast Cultures is held at IFR, where reference strains are maintained and made available to industry. To build on the existing yeast maintenance and identification service offered by IFR, a project is planned to develop and implement new methodology to help generate genetic fingerprints for the different species in the collection. Future studies may enable the IFR to use such genetic information to screen yeast samples for industrially relevant characteristics. Additionally they can offer assistance with problems of fungal contamination and food spoilage.
Last Updated: 04/08/2010 11:29