GlycoLab- Functional Glycobiology
The Functional Glycobiology Lab focuses on understanding carbohydrate (glycan)-protein interactions for discovering novel biomarkers and developing glycan-based therapies and biotechnological applications. We exploit the power of high-throughput glycan microarray technologies to identify functional glycans for proteins at a glycomics scale.
Through an integrative approach, we use structural biology to uncover the molecular determinants of glycan recognition by immunelectins and glycan recognition systems of bacteria and in host-human microbiome interactions. We have a programme for the pre-clinical characterisation of anti-cancer antibodies, collaborating with biopharmaceutical companies.
Unravelling glycan-protein interactions to understand biological recognition systems
CtCBM11 is an archetypal carbohydrate-binding protein from the cellulolytic bacteria Clostridium thermocellum that binds to mixed-linkage β1,3‐1,4‐glucans present in certain dietary fibres and on fungal cell walls. We have used carbohydrate microarrays, X‐ray crystallography and nuclear magnetic resonance (NMR) to establish the molecular basis of CtCBM11 unique recognition mechanism and structurally rationalise its preference for this type of carbohydrates.
The information obtained in this integrative study can be exploited to design new biomolecules with applications in health and biotechnology.
“GLYCOINTERACT: Glycan-human microbiome interaction: glycan diversity and recognition in the human gut with impact on health and nutrition”, FCT-MCTES, Total funding: €234,280, Unit funding: € 176,405 + € 15,625 (NZYTech), Angelina Sá Palma (PI).
“GLYCANTIGENS: Advances in MUC1 Glycan Cancer Antigens: From structure to function in the fight against cancer”, FCT-MCTES, Total funding: €238,195, Unit funding: € 176,266, Angelina Sá Palma (Co-PI).
“INNOGLY, Innovation with Glycans: new frontiers from synthesis to new biological targets”, COST Action CA18103, Angelina Sá Palma (Management Committee member).
“Targeting glycan specificity of tumour-specific antibodies for development of effective anti-cancer strategies”, CRA Siamab Therapeutics, Total Funding: €10,000, Angelina Sá Palma (PI).
Murugesan G; Correia VG; Palma AS; Chai W; Li C; Feizi T; Martin E; Laux B; Franz A; Fuchs K; Weigle B; Crocker PR. 2020. Siglec-15 recognition of sialoglycans on tumor cell lines can occur independently of sialyl Tn antigen expression.. GLYCOBIOLOGY, DOI: 10.1093/glycob/cwaa048
Campanero-Rhodes, MA; Palma, AS; Menendez, M; Solis, D. 2020. Microarray Strategies for Exploring Bacterial Surface Glycans and Their Interactions With Glycan-Binding Proteins. Frontiers in Microbiology, 10, DOI: 10.3389/fmicb.2019.02909
Vendele, I. and Willment, J.A. and Silva, L.M. and Palma, A.S. and Chai, W. and Liu, Y. and Feizi, T. and Spyrou, M. and Stappers, M.H.T. and Brown, G.D. and Gow, N.A.R.. 2020. Mannan detecting C-type lectin receptor probes recognise immune epitopes with diverse chemical, spatial and phylogenetic heterogeneity in fungal cell walls. PLoS Pathogens, 16(1), DOI: 10.1371/journal.ppat.1007927
Gomes, AS; Ramos, H; Gomes, S; Loureiro, JB; Soares, J; Barcherini, V; Monti, P; Fronza, G; Oliveira, C; Domingues, L; Bastos, M; Dourado, DFAR; Carvalho, AL; Romão, MJ; Pinheiro, B; Marcelo, F; Carvalho, A; Santos, MMM; Saraiva, L. 2020. SLMP53-1 interacts with wild-type and mutant p53 DNA-binding domain and reactivates multiple hotspot mutations. BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 1864(1), DOI: 10.1016/j.bbagen.2019.129440
Diana ORibeiro; Aldino Viegas; Virgínia MRPires; João Medeiros‐Silva; Pedro Bule; Wengang Chai; Filipa Marcelo; Carlos MGAFontes; Eurico JCabrita; Angelina SPalma; Ana Luísa Carvalho. 2019. Molecular basis for the preferential recognition of β1,3‐1,4‐glucans by the family 11 carbohydrate‐binding module from Clostridium thermocellum. The FEBS Journal, DOI: 10.1111/febs.15162