Professor Paul Engel BA MA DPhil
Research Interests:
Research carried out by my group focuses on various aspects of enzymes, especially those involved in oxidising amino acids, aiming at a molecular understanding of how they work. Typically this involves obtaining the enzymes in a highly purified state, usually after cloning the gene into a suitable host organism in order to achieve high levels of the enzyme protein.
Some of the work involves studying the enzyme mechanisms, seeking the structural basis of their catalytic activity and in particular aiming for a better understanding of how different protein subunits work together to provide sophisticated regulation of activity - e.g. in the allosteric control of glutamate dehydrogenase.
Other work, supported through Enterprise Ireland's Advanced Technology Research Programme and latterly by a Science Foundation Ireland Fellowship, is focused on practical applications. Modern gene technology makes it possible to alter and adapt enzymes, in search of useful new properties. The chemical industry needs good catalysts, and specifically it needs `chiral' catalysts that can distinguish between left and right-handed versions of chemical molecules. Enzymes are ideal in this regard: they are extremely potent catalysts and they normally give 100% discrimination between left and right. The snag in the past has been that they were too expensive, too fragile and often worked only on the wrong compounds - i.e. biological compounds that might not match the chemist's requirements. This line of research is now producing biocatalysts that are cheap, robust and above all can now work on a wider and more attractive range of chemical targets. This is primarily aimed at producing building blocks for the drug industry. Another application, requiring narrow specificity, is in diagnostic tests and this is being done through a campus company, Enzolve Technologies Ltd. with a focus on neonatal screening.
A third strand of this group's research aims to discover the various ways in which genetic defects in enzymes cause disease. G6PD (glucose 6-phosphate dehydrogenase), is defective in over 400 million people worldwide. The disease mainly affects red blood cells, causing anaemia, and is so prevalent because it coincidentally protects against malaria! Most of the disease mutations affect the long-term stability of the enzyme in the red cell which cannot replace damaged enzyme molecules. We are studying the folding of this enzyme. Another disease-related enzyme under study is IMPDH1. A defect in this enzyme is responsible for progressive blindness in one of the forms of retinitis pigmentosa. This particular form, RP10, shows `negative dominant' inheritance, so that getting the `bad' gene from one parent only is sufficient to cause blindness. The research is aimed at understanding how this happens, with perhaps a chance of finding ways to slow or prevent loss of sight.
Finally, another aspect of the group's research focuses on `extremophiles'; organisms that live in what, to us, seem very hostile environments (i.e. hot, cold, salty). The enzymes of these organisms have to be able to survive the conditions, otherwise the organisms themselves would die. Looking at the molecular adaptations that make this possible teaches us a lot about how proteins work, and some of these tough enzymes have highly desirable properties for practical application.