'Finding out how the enzyme affected in CGD works'
Dr Miriam Hirshberg,
University of Cambridge and Professor Edgar Pick, Sackler School
of Medicine in Tel Aviv, Israel
One year award - £38,754
This research project, due to start in April 2004, will study in great detail
the key enzyme complex (NADPH oxidase; shown below) that is impaired in CGD
and that results in CGD patients being unable to fight certain infections.
They are going to use the most sophisticated and up to date methods available
to help understand how mutations affect the enzymes proper way of working.
They will specifically examine at how the interaction between p67-phox and
Rac components work to activate the oxidase complex leading to the generation
of oxygen radicals and the ability to produce normal microbicadal molecules.
It is hoped that by pinpointing and mapping the most important functional
parts of the oxidase enzyme that therapeutic drugs can be better designed.
UNDERSTANDING THE MECHANISM OF CGD AFFECTED CELLS
Professor Dirk Roos and Dr Cees Otto.
Central Laboratory for the Netherlands Blood Transfusion Service,
Holland
3 Year Project Grant: £124,300
Sophisticated microscopic techniques are being used to study components of
the enzyme NADPH oxidase within live cells representative of human phagocytes/neutrophils.
The group are developing and using probe specific to parts of the NADPH oxidase
enzyme. The probes are tagged with fluorescent markers that show up when
excited with light of different wavelengths. The use of live cells is important
as this means will the NADPH oxidase complex will be analysed in its native,
normal state. The group will determine how certain mutations result in an
inactive enzyme complex that is unable to give a respiratory burst. This
is being done by comparing the localisation of specific proteins in normal
cells versus defective cells using the reagents developed and different microscopic
methods. It is hoped that the information gained will reveal new ways to
regulate NADPH oxidase activity and so lead to new ways to regulate NADPH
oxidase activity.
IMPROVED DIAGNOSTIC TESTING FOR VARIANT CGD
Professor Anthony Segal.
University College, London
2-Year Project Grant: £75,472. Started in April 2003
The purpose of this project is to improve diagnostic testing for variant
CGD as this form of CGD can sometimes be miss-diagnosed. In this form of
CGD the proteins responsible for fighting infection may be able to function
partially but not at a level sufficient to fight off infection. Correct diagnosis
is important for counselling and support of the patient and their family
and for deciding what therapies would be of long-term benefit. A combination
of functional and genetic analyses will be used and this work will lead to
better detection of variant CGD so that early and appropriate preventive
antibiotic treatment can be started. A world expert leads the project and
it is hoped by investigating the genetic mutations present in variant CGD
and how these mutations affect the ability of cells to kill microbes that
drugs to fight infection can be better designed. The information this project
will provide will be entered into the National CGD Registry Database and
will contribute to our knowledge of CGD within the UK.
| gp91phox | p67phox | p47phox | p40phox | p22phox | |
| CGD Patient |  |
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| Healthy Control |  |
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| This figure shows the results of a diagnostic test of a patient lacking the gp91phox and p22phox components of NADPH oxidase. | |||||
IMPORTANT NOTE :
The information contained on this website is intended only as a guideline, not as a substitute for medical advice. Always consult your doctor if you or your child has any CGD symptoms or concerns.
© 2001-2005 The Chronic Granulomatous Disorder (CGD)
Research Trust
Registered Charity No. 1003425 email:cgd@cgdrt.co.uk
The CGD Research Trust is a member of the Association of Medical Research Charities (AMRC), the Genetic Interest Group (GiG) and an associate member of the International Patient Organisation of Primary Immunodeficiencies (IPOPI)
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