Endoplasmic Reticulum function / structure in neuronal (patho)physiology
Cells of high organisms compartmentalise a variety of biochemical milieus in several membrane-enclosed organelles (nucleus, mitochondria, endoplasmic reticulum etc.) each shaped and equipped to perform its specialised function(s), endowing the organism with almost unlimited functional versatility. The Endoplasmic Reticulum (ER) is an assembly of perinuclear membranous sheets interconnected with a contiguous network of tubes extending throughout the entire cell periphery. The functions of this organelle encompass manufacturing of secretory/membrane proteins and lipids, calcium storage, detox and distribution of bioactive substances to the cell periphery.
Understanding of how the multitude of ER functionalities is supported by its intricate and highly dynamic structure is crucial for rationalising the abundantly evident sensitivity of the neuronal system in particular to the perturbations in ER functionality (prominently exemplified by a causative association of ER morphogens, aka ER shaping proteins, with neuropathologies such as Hereditary Spastic Paraplegia and their involvement in dementia).
We seek understanding of how the ER's function-structure relationships play out in neuronal cells' normal functioning and disease, with the long term goal of identifying targets for pharmacological intervention to prevent/modify neurodegeneration occurring in dementia e.g. Alzheimers and Parkinson's disease, and that of genetic disorders such as Hereditary Spastic Paraplegia. In our quests, we rely on the combination of techniques such as high tempora-spatial resolution light microscopy, genetically encoded biosensing, cell genetic manipulations tool and in vitro/in vivo biochemistry. These are implemented in cell-based diseases models such as neuronal tissue culture of CRISPR/Cas9 genome-edited induced pluripotent stem cells (iPS cells).
E R – R e d o x / R O S
We use and develop genetically encoded probes for monitoring RedOx/ROS in live cells to advance the understanding of ER’s role in health and diseases associated with oxidative stress.
P r o b i n g a g g r e g a t i o n
To better understand cellular machinery involved in handling protein aggregation, a process accompanying dementia, we develop and implement techniques for optical monitoring of protein (dis)aggregation in live cells' organelles