⭘ OVERVIEW

Proteins are the primary effectors of cells. They are highly organized in a variety of assemblies, forming the basis of well-regulated pathways and networks to precisely execute a plethora of cellular processes. Alternations of proteins expression, and their interaction networks are linked to many physiological and pathological conditions.

Alison's research currently focuses on the modulation of protein secretion by mammalian cells and how this may relate to the treatment of diseases linked to aberrant secretion. Using her expertise in advanced microscopy, her team studies the effect of modulation of the early secretory pathway on cellular homeostasis and protein secretion. Alison's research is interdisciplinary, and she works with collaborators to identify new modulators of the secretory pathway and their mechanisms of action. Alison is expert in advanced bio-imaging techniques, including light sheet array microscopy and high-resolution confocal microscopy, using state-of-the-art technologies now available at the University of Namur's imaging platform ("MorphIM").

To carry out this work, she obtained a research position at the University of Namur (F.R.S-FNRS Chercheur Qualifié). An episode of Z Science is dedicated to her.

⭘ OUR FOCUS

The exit of proteins from the endoplasmic reticulum (ER) is a crucially regulated step in the early secretory pathway. ER exit sites (ERES) are responsible for sorting cargo into COPII-coated transporters, for transport to the Golgi apparatus. This is a highly dynamic process, regulated by the orchestration of a number of proteins on the outer edge of the ER membrane. We recently discovered the first pharmacological inhibitor of ERES, Retro-2. Using Retro-2 as a tool to study acute ERES inhibition, and as proof of principle that ERES can be targeted, my project proposal addresses three questions:

  1. How does Retro-2's target, the ERES component protein Sec16A, mediate ERES function and cargo selection?

  2. What is the effect of acute modulation of ERES on organelle and cell homeostasis?

  3. How can ERES be developed as a therapeutic target?

By combining basic research into the regulation of ERES function and the application of this novel tool to cell/tissue homeostasis and disease, my group will combine interdisciplinary approaches (structural biology, mass spectrometry, interactomics, advanced bioimaging and medicinal chemistry) to provide a solid foundation on which we will develop ERES as a novel therapeutic target.

⭘ DRUGGING THE ERES