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EPSRC Reference: EP/C546555/1
Title: A new approach for ensuring the biocompatibility of medical devices - molecular breeding of enzymes for preventing S. epidermidis biofilm formation
Principal Investigator: Wilson, Professor M
Other Investigators:
Nair, Dr SP Pratten, Dr JR
Researcher Co-Investigators:
Project Partners:
Department: Eastman Dental Institute
Organisation: UCL
Scheme: Standard Research (Pre-FEC)
Starts: 14 November 2005 Ends: 13 November 2008 Value (£): 202,304
EPSRC Research Topic Classifications:
Biological & Medicinal Chem. Chemical Biology
Med.Instrument.Device& Equip.
EPSRC Industrial Sector Classifications:
Related Grants:
Panel History:  
Summary on Grant Application Form
An exciting aspect of modern medicine is that we now can make spare parts to replace parts of the body that have worn out or have been damage in some way. For example, we can make artificial hips, knees, heart valves and voice boxes. We also use a number of tube-like devices (known as catheters) to deliver fluids (containing nutrients or various drugs) to seriously-ill patients or to remove fluids (e.g. urine) from such patients. Unfortunately, bacteria from the skin can stick to these devices and grow to form structures (known as biofilms) consisting of millions of bacteria surrounded by a jellylike material. Inside these biofilms, the bacteria are protected by the jelly from the body's defence systems as well as from antibiotics. Therefore, once biofilms have formed on these medical devices, they are very difficult to remove and they eventually cause an infection which can kill the patient. In this project we are going to try to use enzymes that can break up the jelly-like material so that the biofilms can't be produced in the first place or can be broken down once they have formed (they will therefore no longer be protected can then be killed by antibiotics). The problem is where can we get such an enzyme from? It would have to be able to work very quickly, do the job at low concentrations and work under the conditions found in the body. There may be an enzyme somewhere on the planet that would be ideal for the job, but it would take a long time to find it. What we intend to do is to produce a super-enzyme that can very rapidly and efficiently break up the biofilms or prevent the biofilms from forming in the first place. To do this we will need to start with the genes that carry the information for enzymes that could break up the biofilm - but that are not good enough to use to treat patients because they work too slowly, or else because we'd need very high concentrations or because they wouldn't really work under the conditions present in the body where the biofilms form. From these we will breed the superenzyme we're looking for. To do this we will chop up each of these genes into small sections and then mix them all up and then join the bits together again in different ways. This will give us thousands of different enzymes, some of which are certain to be very good at destroying biofilms or preventing them from being formed. Once we've got these enzymes we can test them to find out which of these has the properties we're looking for. We can then use one of these to coat the spare part or the catheter before the doctor inserts it into the patient - this will protect the patient from biofilms. Or else, we can inject the enzyme into a patient who already has an infection due to a biofilm and therefore cure the patient of the infection.
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