Dr David Gershlick

Characterising the secretory pathway machinery

Defects in protein trafficking are a causal factor of incurable, neurodegenerative disorders such as Parkinson’s and Alzheimer’s diseases. Despite the great efforts made in the last 20 years to study intracellular protein trafficking, there are still gaps in our understanding of these pathways. Understanding the complexity of protein sorting pathways is critical for the potential future development of new therapies. 

One example of a poorly understood trafficking pathway is the secretory route from the Golgi apparatus to the plasma membrane. The secretory route from the Golgi, represents a major transport route of transmembrane proteins and soluble proteins from their site of synthesis in the ER. This secretory route also has an important role in human diseases as cytokines, lipoproteins and antibodies are all secreted in this manner.

In previous work (http://jcb.rupress.org/content/216/12/4141) we have been able to reproducibly visualise tubules that bud from the Golgi apparatus with a high spatio-temporal resolution. 

Our lab is using this strategy and others to understand the secretory machinery in more detail. This will be accomplished by investigating and probing the kinetics of the known secretory components and by identifying new proteins and lipids that form and traffic in Golgi tubules.

To achieve these goals the lab uses a number of different and complementary approaches including confocal microscopy, super-resolution microscopy, biochemistry, proteomics and lipidomics.