B Loos, J-HS Hofmeyr, KK Müller-Nedebock, L Boonzaaier, C Kinnear in Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging (ed. MA Hayat) 3, 39–56 (Elsevier, 2014). DOI: http://dx.doi.org/10.1016/B978-0-12-405529-2.00002-0
Dr Ben Loos (Dept of Physiological Sciences at Stellenbosch University) has a long-standing interest in the molecular mechanisms that control cell death susceptibility. His research centres around protein degradative mechanisms and their dynamics, transport and function of mitochondria along tubulin networks and their role in neuronal degeneration and migration. His research group utilizes in vitro models for neuronal protein aggregation storage disorders such as Alzheimer’s disease, to unravel and to direct the complex molecular interplay towards an environment that favours cellular function and survival. He has an equally long-standing interest in high resolution fluorescence-based microscopy techniques, and has managed the Cell Imaging Unit (www.sun.ac.za/saf) for many years. Integral part of his research in physiological sciences is the application of powerful microscopy techniques such as SR-SIM.
The organisation and dynamics of intracellular structures that maintain a cell’s form, shape, function and viability are rather complex. An emerging central theme which addresses this complexity deals with ATP-driven intracellular transport mechanisms along the tubulin network or the ability of mitochondria to rapidly undergo fission and fusion, and thereby creating a network that is adapted to the required ATP demands of the cell. In many physiological disorders, such as neuronal degeneration, these processes are disturbed, leading to increased cellular susceptibility to undergo cell death.
Physics modelling can add meaningful insight into the above processes. For example, semi-microscopic theories for membrane energetics and fluctuations can be utilised to understand the fusion between organelles. Descriptions including simple and driven – or active – dynamics of fusion and separation processes are possible. Predictions on transport processes and collective activity are accessible through nonequilibrium statistical physical treatments. On a slightly larger scale the insights from the fusion can be applied to network modalities. Here theoretical physical and mathematical characterisation of network properties would certainly assist in the analysis of experimental data.
For example the phenomena associated with autophagy can be studied through a variety of approaches. We recently published a chapter “Autophagic Flux, Fusion Dynamics, and Cell Death” that shows how physics modelling can be added to the understanding of this process, understanding of which might ultimately help science to understand a variety of disorders.
The Nanobiophysics-SU group is particularly interested in the emerging field of organelle network analysis related to properties such as elasticity, connectivity and efficiency that report on molecular interactions and cellular function. A unique approach lies in the nested approach of theory and experimentally derived data on the nano-scale. By plugging into the power of molecular imaging technologies such as structured illumination superresolution microscopy (SR-SIM), this group addresses questions that arise only at the interface of nanotechnology and biology. SR-SIM allows to resolve specifically labelled structures down to 80 nm. Current projects address fusion dynamics between autophagosomes and lysosomes, mitochondrial network connectivity and actin-cyctoskeletal stiffness. For example, microscopy data together with physics models for networking and organelle structure can help to cast light on the dynamics inherent to mitochondrial networks numerically. The predictive power that this interdisciplinary approach allows to generate, is highly valuable for both biology and theoretical statistical physics alike.