Roles of PI 3-kinase isoforms in autophagy and endosomal membrane dynamics

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One of the most fundamental component parts of the human body is a structure termed a cell. Every cell is surrounded by a membrane of fat which maintains its identity separate from the surrounding environment. Furthermore, every cell is subdivided into more compartments by itself containing discrete and unique membrane-bound structures termed organelles. In order for a cell to function it must be able to perform a number of roles including communication with the extracellular milieu, the regulated transfer of material between organelles and the recycling of aged material within the cell itself. Defects in any of these functions can lead to abberations which ultimately cause the cell to malfunction and lead to cancer, the unregulated growth of cells. Our laboratory works on catalysts within the cell termed PI3Ks. PI3Ks are able to specifically manipulate the composition of the cellular membranes. These manipulations are critical to ensure fidelity of the transfer of material between organelles and between the external environment and organelles. The importance of these PI3Ks in maintaining normal cellular functions is highlighted by the fact that they are compromised in a high percentage of tumors. Consequently it is obvious that if we wish to tackle the causes of cancer and try to cure patients suffering from cancer it is vital that we know how PI3Ks function in whole organisms. The main problem with this avenue of enquiry however is that there are numerous flavors of PI3K within cells and each performs a distinct role within the cell. To this end our laboratory generate mice models where the activity of discrete PI3Ks are specifically ablated, both at the level of cells and the whole organism. By this methodology we are able to assign specific roles to each PI3K and in combination with drug companies design small molecule inhibitors targeted towards each PI3K. These small molecule inhibitors are then tested in directed experiments to see whether they will be of any therapeutic use in tackling cancer and other health issues arising from defective PI3K signalling.