Elements of a Vesicle Machine

Despite cells being thought of as the smallest unit of life, they are actually made up smaller components that give them the ability to perform functions such as self-repair, and produce and harness energy. These components consists of large collections of proteins and lipids, the building blocks of cells, that actually work together to create higher level functions. A useful analogy is that of a city and a cell. A city often requires a wall (an outer lipid membrane), power plants (mitochondria from animal cells, and chloroplasts from plant cells) and factories and engineering firms to repair the city infrastructure (lipid homeostatic machinery). Each of these units is run by workers and machinery (lipids and proteins).In this project, we aim to take apart cells, but not at the level of the workers , instead at the level of the city infrastructure and bring them back together in a different combination with a view to constructing a new city (novel self-assembling micron scale machinery). These components, that we will be 'hi-jacking' from cells will be housed within artificial lipid vesicles that will provide a housing which mimics the ability of cells to ring-fence and protect their infrastructure. It is not yet known which components can be coupled in this manner and this is something that we aim to explore.

Our goal is to explore the feasibility of generating hybrid, self-sustaining microscale machinery (HSSMMs) using an approach which is distinct from any other grouping. We will combine and manipulate gross elements of cellular machinery including mitochondrial organelles, lipid biosynthetic machinery and ion channel couples into lipid vesicles. We aim to demonstrate that these elements are isolatable and can constitute systems in their own right that can be coupled to create systems that are paradoxically more than the sum of the whole. Whilst replication is fundamental to the property of any living cell, here we choose to disregard this aspect and concentrate solely upon the ability of the HSSMMs to act as power sources that can be coupled to external systems and adapt to changes in their external environment. We believe that our high risk strategy of commandeering isolated components of the cell machinery and quantifying the interdependence of these modules will have wide ranging implications in the academic community and beyond. It would represent a novel approach, distinct to that of Synthetic Biology. In the short-term (12-18 months), the cross-disciplinary approach that is vital to tackling this strategy will bring together researchers within and thereby strengthen the cross-disciplinary networks at Imperial College, in particular the Chemical Biology Centre (CBC) and the Membrane Biophysics Platform (MBP). These feasibilities studies and their continued long term exploitation (24 months-10 years) will stimulate involvement in disciplines of chemistry, engineering, physics, mathematics, biophysics and biology. In addition to the standard methods of dissemination, meeting conferences and peer reviewed publications, we will make extensive of the MBP online Sharepoint facility and continue to organise 'Ideas Workshops'. The latter two have proven to be excellent methods of dissemination and already link over 60 research groups. In the longer term (10-15 years), HSSMMs capable of using light or mitochondrial organelles to generate ATP, which can be used as an energy currency, have the potential to revolutionise power sources for Micro-Electrical-Mechanical Systems (MEMs). By demonstrating the feasibility of first generation HSSMMs we will unlock the potential for more complex systems that can underpin novel in-vivo delivery and biosensor applications in the healthcare sector. Whilst these applications are somewhat in the future, it is vital that we capture the new IP and identify killer applications by engaging early on with the industrial sector, both during and after the feasibility studies. Our patent strategy through IC Innovations, will allow us to protect this new IP before engaging the community via established routes such the Technology Strategy Board Knowledge Transfer Networks and the CBC Technology Showcase events. The project and its deliverables sit within three of the priority research themes of the EPSRC (Nanoscience Through Engineering to Application; Energy; Towards Next Generation Healthcare). The two early careers researchers, the key resource for these studies will acquire extensive experience of systems integration and technology transfer, transferable skills that are vital to the continued future success of the academic, biotechnology and nanotechnology sectors. This exciting project is likely to stimulate increase public awareness of nanoscience. We will capitalise upon this by commissioning audio-visual content associated with our feasibility studies (e.g. recording of conference lectures or school lectures); these will then be uploaded onto facilities such as iTunesU and YouTube so that the general public can freely download this material.