Non-Markovian models of intracellular transport in a heterogeneous environment

Transport of all kinds of components within the cell - from vesicles along the cytoskeleton through to transcription factors along DNA - is fundamental to cell function and health. Neurons are particularly susceptible to small changes in vesicle transport, which underlie motor neuron disease and may also contribute to neuronal degeneration seen in Alzheimer's disease and during ageing. Despite experimental facts that intracellular transport is heterogeneous and non-Markovian with subdiffusive and superdiffusive regimes most mathematical models for vesicles trafficking are Markovian and homogeneous. The main challenge for our Manchester interdisciplinary team is to obtain new non-Markovian models of heterogeneous intracellular transport supported by experiments. These models will provide a tool set for analysing transport processes in a much more realistic way, opening the way for greatly improved analysis and ultimately understanding of these highly complex cellular behaviours. This will allow other researchers to formulate and test new hypotheses. In the long term, therefore, non-Markovian models have the potential to lead to insight into neurological diseases, ageing and other processes that involve intracellular transport such as bacterial and viral infection. Such knowledge will be important for developing new treatments. Our project combines three different approaches: mathematical modelling, numerical modelling and experimental validation, which complement each other. This strategy will provide multidisciplinary study of the intracellular transport problem and ensure maximum impact across and within several disciplines. Our project will allow applied mathematicians (PI and RA), cell biologists and biophysicists (Co-Is and Project Partners) to collaborate thus making significant advances in intracellular transport research and support a cross-disciplinary dissemination.