The GLYCO-N envisions a multifaceted chemical biology approach by two scientific work packages (WPs), one (WP4) on viral N-glycosylation and another (WP5) on N-glycosylation in archaea and microalgae. The work ethos in both WPs is the same and encompasses the following elements. In the explorative phase, microbiology studies on selected model species will identify N-glycoproteins and their processing enzymes, whose structures (N-glycoforms, glycosyl transferase (GT) and glycoside hydrolase (GH) families) will be resolved in molecular detail by structural biology (NMR, X-ray, EM) and bioinformatics. Synthetic organic chemistry guided by computational chemistry will then provide the tools to capture and study GT/GH mode of action and, for the exploitive phase, yield modified substrates for glycan engineering and lead-inhibitors for antivirals.

The scientific knowledge acquired in these two WPs will be complemented by additional research and transferable-skills courses in a structured program through networking sessions, secondments to our associate partners, and other training and outreach activities. Importantly, since the GLYCO-N DCs will be exposed to different disciplines, they will contribute to both scientific WPs. For instance, deciphering a new N-glycan may lead to the discovery of a new glycoprocessing enzyme (GT/GH) and from there to the development for new antivirals strategies, but also for new N-glycan biomaterials design.

In addition, a glycomimetics design and synthesis campaign may be boosted by structural insights into glycan-processing enzyme inhibition.

WP Organization of GLYCO-N

WP4 Viral N-glycosylation.
Lead by BIO, Prof. Jesus Jímenez-Barbero

This WP will focus on the two general pathways by which viral capsid proteins become N-glycosylated. It will take into account “regular viruses”, being viruses that recruit the host N-glycosylation machinery to N-glycosylate their capsid proteins; and “giant viruses” that recently and surprisingly have been discovered to have their own N-glycan biosynthesis system.


WP5 Archaea and microalgae N-glycosylation.
Lead by UDE, Prof. Bettina Siebers and Markus Kaiser

In this scientific WP, selected archaea and microalgae will be examined for their N-glycans, by looking into their structural diversity, their biosynthesis/turnover and their function.

Work Package 1 – Immune regulation

WP1 is led by Dr. Niloufar Safinia of Kings College London, United Kingdom.

WP1 explores ECP as an alternative form of induction therapy to avoid high-dose immunosuppression early after transplantation. ECP is clearly effective in suppressing T cell-mediated pathologies, including acute GVHD, so we expect that ECP can also suppress T cell alloimmunity after solid organ transplantation, reducing the need for early high-dose immunosuppression. Consequently, we see important potential applications for ECP induction therapy in patients who might benefit from avoidance of conventional immunosuppression in the immediate post-operative period; for instance, in transplant recipients at high risk of transplant-related infections (Gökler, J. Transpl Int. 2022) or liver transplant recipients vulnerable to CNI-associated renal failure (Urbani, L. J. Clin. Apheresis. 2007; Schnitzbauer, A. Transplantation. 2015). Interestingly, it has been claimed that ECP restores immune homeostasis through diverse immunoregulatory cell subsets, including regulatory T cells (Tregs), regulatory B cells (Bregs), ‘modulated’ NK cells, myeloid-derived suppressor cells (MDSC) and tolerogenic dendritic cells (DC). Therefore, ECP induction therapy could also be useful in establishing allospecific immune regulation early after transplantation. WP1 tackles ECP induction therapy through subprojects at world-class clinical research labs focusing on Tregs (DoC1), NK cells and MDSC (DoC2) and Bregs (DoC3).

WP2 considers the impact of ECP on humoral immunity. It is known that ECP reduces donor-specific antibody (DSA) titres in heart, lung and kidney transplant recipients (Benazzo, A. Transfus Med Hemother. 2020). However, ECP seems not to impair protective antibody responses and it’s not an effective treatment for classical antibody-mediated autoimmune diseases, such as myasthenia gravis. The most likely explanation for this differential therapeutic effect is that ECP suppresses T cell-dependent antibody production by memory B cells, but can’t suppress antibody production by long-lived plasma cells.

Antibody-mediated allograft injury is a major contributor to acute and chronic transplant dysfunction and loss, which is poorly controlled with current immunosuppression. Through 3 subprojects in outstanding basic or clinical research groups, WP2 addresses potential applications of ECP in preventing antibody-mediated rejection (ABMR) in kidney transplant recipients and preventing chronic lung allograft dysfunction (CLAD) in lung transplant recipients with persistently elevated DSA.

Work Package 2 - Antibody responses

WP2 is led by Anja ten Brinke of Stichting Sanquin Bloedvoorziening, Amsterdam, the Netherlands.

Work Package 3 – Tissue repair

WP3 is led by Prof. Elke Eggenhofer of University Hospital Regensburg, Germany

WP3 explores the potential for ECP to resolve tissue damage by suppressing early innate inflammation or stimulating tissue-repair. Unlike applications of ECP in inflammatory disorders, using ECP to directly promote repair processes has not been previously investigated. WP3 builds upon basic scientific discoveries showing that monocytes exposed to apoptotic cells acquire tissue-reparative properties, as well as evidence from patients with acute liver injury or liver transplants, showing the importance of tissue-repair macrophages in resolution of extensive liver damage (Moroni, F. Nat Med. 2019). We see impactful clinical indications for ECP in preventing inflammation after ischemia-reperfusion injury (IRI) and as a potential “bridging therapy” for patients with acute liver failure who are wait-listed for time-critical liver transplantation

WP4 is a preclinical research package that aims to develop and validate in vitro diagnostic (IVD) assays for pharmaceutical testing of photopheresates, as well as pharmacological monitoring of responses to ECP in organ transplant recipients. WP4 will also explore the hypothesis that the living cell fraction and acellular components of photopheresates also exert clinically important effects.

Work Package 4 - Immune pharmacology

WP4 is led by Prof. Holger Hackstein by Univ. Hospital Erlangen, Germany