Physicochemical analysis of the potential for liquid condensation via liquid-liquid phase separation in the Golgin family of proteins

• Grant number: 23/13459-3
• Support Opportunities: Scholarships in Brazil - Master
• Start date: February 01, 2024
• End date: January 31, 2026
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Luis Felipe Santos Mendes
• Grantee: Igor dos Santos Pedriz
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
• Associated research grant: 22/06006-0 - Elucidating the impact of functional protein liquid and solid condensates in the secretory pathway, AP.GR

Abstract

The Golgi complex plays a central role in the cell and is crucial for protein sorting, transport, and lipid metabolism. This organelle is characterized by stacked, flattened cisternae, displaying a notable polarity between its cis and trans faces, each responsible for different stages of protein maturation and transport. The integrity and organization of the Golgi are upheld by the Golgi Matrix Proteins (GMPs), predominantly composed of golgins and GRASPs. These proteins not only ensure the unique structure of the Golgi but also the correct localization of resident enzymes, vital for the proper processing of proteins. Although the discovery of the Golgi complex dates back over a century, the mechanisms that define its structure remain a mystery. Recently, the formation of biomolecular condensates has emerged as a strategy adopted by cells to organize their internal space. Recent research, including ours, suggests that the condensed arrangement of the GMPs may directly influence the structure of the Golgi. However, due to difficulties working with members of this protein family, there is currently no structural/biophysical study in the literature involving a complete construction of golgins from any organism. Aiming to address this gap, the main objective of this master's project will be to innovatively understand the physicochemical process that regulates the formation of liquid droplets generated by LLPS of a golgin (BUG1 - Binder of USO1 and GRH1 protein 1). This physicochemical approach in a high-throughput mode will be a groundbreaking study in the literature and will have a significant impact on understanding the structure and organization of the Golgi.