Zhang Dan’s lab studies the dynamics, formation and functions of intracellular membrane junctions. The lab is working to uncover the molecular basis and physiological consequences of the endoplasmic reticulum (ER) structure and dynamics, including the ER morphogenesis, its organelle contacts and cytoskeletal interactions by deploying multiple models and disciplinary approaches. These include model organisms of S. pombe, C. albicans, C. elegans, and yeast/worm genetics, biochemical tools, high-resolution live-cell imaging, microfluidics, omics, mathematical modelling and machine-learning techniques, to name a few.

Using yeast, Zhang Dan was able to discover a class of conserved proteins for membrane junction formation and regulation. She also revealed their important roles in maintaining cell polarity and regulating cell division. Interestingly, it was found that these proteins have been implicated in human motor neuron diseases. In particular, VAPs, the major players for membrane junction formation, are associated with amyotrophic lateral sclerosis type 8 (ALS8).

The endoplasmic reticulum (ER)-plasma membrane (PM) contact sites, thought to function in lipid trafficking and calcium signalling, are particularly prominent in yeast, plants and excitable cells in metazoans. A group of evolutionary conserved membrane integral proteins have also been identified to couple the ER and PM in various model systems. However, underlying mechanisms of the ER/PM contact formation remain poorly understood. Zhang Dan’s lab aims to uncover how these and potentially other proteins function in mechanistically tethering the ER to the PM.

The functions of ER/PM contacts in calcium and lipid homeostasis, as well as their potential involvement in the PM patterning and cell stress response, require further investigation. How the PM-vesicle crosstalk involves in the polarity and shape maintenance of fission yeast and other pathogenic fungi is also of interest.

Looking ahead, Zhang Dan hopes to initiate industrial projects for developing yeast-based synthetic biology tools, and expand the lab’s research focus into human fungal pathogen studies. Studying molecular cell biology of human pathogen provides essential insights into key components that define infections.