Cells increase their mass during proliferation and differentiation, which must be accommodated by plasma membrane expansion. Membrane growth is essential to accommodate increases mass and cell growth. As such, lipid synthesis and transport are functionally coupled to cellular metabolism and must be tightly coordinated to permit membrane growth. Neurons are great examples of this; Growth factors signalling results in dramatic membrane and cell growth, producing complex, intricate networks of neurites. 

Growth factor signalling therefore drives lipid synthesis, which must be coupled with transport of lipids to target membranes. While vesicular transport pathways are well-studied mechanisms for membrane lipid delivery, non-vesicular mechanisms are also essential. However, we don’t know the relative contributions of each pathway. It is unclear how these mechanisms are coordinated during cell growth, and what the necessary machinery is. Furthermore, mutations in proteins involved in non-vesicular transport, such as the ER-organelle tether VAPB, lead to neurodegeneration, highlighting how loss of non-vesicular lipid transport mechanisms leads to membrane growth impairment and cell death. My project aims to understand how membrane lipid synthesis and transport is coordinated to drive neurite growth, and how these mechanisms are disrupted in neurodegenerative disease.