Cells perform their functions in the body using sophisticated molecular machines. These machines are uniquely assembled protein complexes with a dimension of a few nanometers, which is a millionths of a millimeter. Elucidation of the structure and function of these machines is the basis for a mechanistic understanding of cellular functions from signal processing to muscle contraction.
The central project in our laboratory is currently the investigation of the molecular machine, which releases many neurotransmitters and hormones in the body. Like a motorized door opener, this machine opens a door allowing release of transmitter molecules from tiny storage compartments, the secretory vesicles. To determine how this works, we combine experiments in which we characterize the opening of these doors using specially developed microfabricated devices with computer simulations that visualize the molecular mechanics. Tetanus toxin destroys essential components of this machine and the widely known BoTox treatment modifies this machine and thereby reduces transmitter release. The precise understanding of the molecular mechanics may lead to new treatment strategies. It will also advance our understanding of the mechanisms by which viruses such as Influenza and Corona Virus enter cells because they use closely related mechanism.
Fusion pore formation between a nanodisc and a bilayer.
Coarse-grained simulation trajectory of membrane fusion pore formation and its subsequent closure. Water density at the fusion site is shown as cyan surface. From Sharma & Lindau (2018) PNAS 115: 12751-6