CATSIG: Synthesis and study of catalytic signalling systems to create vesicles that mimic cell sensing and signalling
Lead Research Organisation:
University of Sheffield
Department Name: Chemistry
Abstract
A critical feature of complex biological systems is the compartmentalisation provided by lipid bilayer membranes. This separates the inside and outside solutions and allows otherwise incompatible chemical processes and networks on the interior and exterior to co- exist independently. However, it is critical that extracellular molecules, such as hormones, nutrients and pathogens, can change the intracellular chemistry - and this is achieved by signalling across the cell membrane, usually via membrane-spanning proteins, which trigger a cascade of reactions which both amplify and transduce the original signal so that the cell can respond appropriately. Vesicles are simplified analogues of cells, and have the potential to store, amplify, transduce and communicate information in the same way, and this proposal aims to functionally mimic the cellular response with entirely synthetic systems. The aim is to couple an external molecular recognition event with an internal catalytic process using a novel transmembrane signal transduction pathway. Vesicles are already used in drug-delivery applications, but there is huge potential for responsive vesicles - those that can react in a specific and targeted way to an external signal such as a molecular binding event - which could be used in targeted drug delivery, such as the catalytic activation of a pro-drug for controlled-release applications. Furthermore, multivalent vesicles that are capable of efficient transduction of chemical information will provide a platform for the construction of biocompatible interfaces for communication with cellular systems for sophisticated sensing applications and diagnostics.
Organisations
| Description | We have discovered that we can synthesis a transducer that is far more reactive than all the currently reported systems. These act on less reactive substrates, and we have a greater insight into the catalytic cycle, which is allowing us to expand the substrate and how the system can be created. We have discovered that repeating previously reported methods of creating inert systems are not reliable - probably because our new system is far more reactive. We have combined our new catalytic centre with a new method of controlling the active state, and have shown that it is reliable and effective. This has allowed us to cycle the system through on and off states and demonstrate turnover for the first time. We have also established that we can create an effective system with both membrane embedded and solution based transducers. This extends the kinds of systems that can create to much greater versatility. |
| Exploitation Route | There has been increasing interest in these types of systems, and so we expect that our new catalytic groups will directly affect others working on related systems. We are in the process of publication as the final discoveries were made very late in the project, but will provide the most meaningful impact to publish first. The greater understanding, effectiveness and accessibility of the materials we have now made will allow others to incorporatethem into complementary systems, or to use our systems as part of more complex assemblies. |
| Sectors | Chemicals Healthcare Pharmaceuticals and Medical Biotechnology |