Dissection of protein interactions in the context of glycosylation
Navn på bevillingshaver
Adnan Halim
Institution
University of Copenhagen
Beløb
DKK 4,973,007
År
2021
Bevillingstype
Semper Ardens: Accelerate
Hvad?
The research project is about a class of sugar molecules (glycans) that, together with DNA, proteins and lipids, constitute the basic molecular components of cells. Proteins execute distinct biological functions in cells, and mature proteins on the cell-surface are often modified by glycans (glycoproteins). We recently discovered a new type of glycan based on mannose sugars (O-Man) which are attached to distinct cell-surface glycoproteins that control cell-cell interactions and communications. Our hypothesis suggests that the new type of O-Man glycans diversify glycoprotein functions, fine-tune interactions and regulate cell-cell communications.
Hvorfor?
Cellular functions are often orchestrated by macromolecular machineries composed of many different proteins. While great progress has been made towards understanding how proteins form functional machineries, far less is known about how glycans influence this process, and insight into how the new types of O-Man glycans influence protein interactions is completely lacking. Importantly, genetic deficiencies in O-Man biosynthesis is known to cause severe congenital disorders and early childhood deaths, clearly stressing the critical, but as yet unknown, biological functions of O-Man glycans. This research project aims to bridge this knowledge gap and address current limitations in the understanding of how cell-surface glycoproteins interact and execute their functions.
Hvordan?
The overarching aim is to adopt a multidisciplinary approach combining precise genome editing (CRISPR/Cas9) and advanced mass spectrometry to decipher the functions of O-Man glycans in human cell lines. A primary objective is to develop new analytical tools to overcome current roadblocks in mass spectrometry-based analysis of glycoproteins. We will address an important unmet need for new, innovative solutions capable of resolving glycoprotein interactions in the context of their glycosylation status. The outcome is predicted to lead to new concepts in analytical glycobiology and fill a major knowledge gap in cell biology.