Glycans, carbohydrate structures widely present on cell surfaces, play crucial roles in various biological processes, such as cell signaling and neoplasia. However, research on glycans faces challenges, including limited access to biologically relevant synthetic forms and technical difficulties in analyzing glycan-protein interactions. Additionally, glycans play essential roles in viral infections, facilitating virus attachment and entry. Notably, human noroviruses (HuNoVs) are the primary causes of viral gastroenteritis and foodborne illnesses, resulting in significant morbidity, mortality, and economic losses.
While NoV infections typically resolve on their own in healthy individuals, they can lead to severe complications in those with weakened immune system, the elderly, and young children. Moreover, the emergence of new NoV genotypes and variants often triggers large outbreaks and epidemics globally. Understanding NoV infections in non-human hosts remains limited, yet the genetic similarities between some animal and human NoVs suggest the potential for cross-species transmission, potentially leading to pandemic variants. Despite the urgency, there are currently no therapies available to treat or prevent NoV infections. Crucially, the necessity for NoVs to attach to specific glycans for infecting host tissues and cells is well-known, although the exact mechanisms involved remain unclear.
Belonging under the Work Package 2 (WP2) of the GlycoNoVi project, the doctoral research project aims to build a library of well-defined high-purity HBGA (histo-blood group antigen) glycans and epitopes. Bioinformatics searches coupled with wet-lab screening will be used to identify novel glycosyltransferases that can functionalize core glycan structures with a variety of degree of polymerization and to create HBGA epitopes. The best enzymes will be taken further into enzymatic and fermentative synthesis routes to obtain glycans in amounts sufficient for small scale purification. This will lead to a glycan library complementary to WP1 library and that will be used in further in vitro screening and can be chemically derivatized further (in collaboration with WP1) for in vitro screening. Planned secondments at EMC (Erasmus Universitair Medisch Centrum, Netherlands) and CSIC (Agencia Estatal Consejo Superior De Investigaciones Cientificas, Spain) aim to screen the potential glycan structure for antiviral applications and gain insight into the structural interaction mechanism.