The journey into the Glycosciences Field

I am a Research Assistant Professor at the Faculty of Science and Technology, NOVA University of Lisbon (FCT-NOVA), Portugal and an integrated member of the UCIBIO (Research Unit on Applied Molecular Biosciences, http://www.requimte.pt/ucibio/people/angelinapalma). I obtained my degree in Biochemistry in 2001 at University of Algarve, Portugal, and completed the PhD degree in Biochemistry in 2007 at NOVA University. 

During my pre-doctoral and PhD studies at the Laboratory of Glycobiology, ITQB-NOVA, under the Supervision of Dr Julia Costa, I was trained in fundamentals of glycobiology and of glycosylation pathways in mammalian-, insect- and plant-cells, and learned about the important role of glycans and their recognition in all domains of life, and also in health and disease processes.

I joined the Glycosciences Laboratory of Prof. Ten Feizi (Imperial College London), first as visiting scholar (2004-2005) during my PhD and thereafter as a post-doctoral fellow (2007-2009), funded by the Portuguese Foundation for Science and Technology (FCT). While at the Glycosciences Lab, I developed pioneering work in designer glycan microarray approaches to study glycan recognition systems of biological and biomedical impact and in the setting-up of a state-of-the-art glycan-microarray system and in its application to glycan-ligand discovery. During this period I was trained in fundamentals of glycan chemistry, lectin- and immune-recognition, and methods for glycan analysis, including mass spectrometry to structurally characterize glycans. At present, I am an Honorary Research Associate of Imperial College London, working with colleagues at the Glycosciences Lab in developing further the glycan microarray technology and its applications (http://www.imperial.ac.uk/people/apalma/).

Taking advantage of my 6-year post-doctoral fellowship from Portuguese FCT, and with the aim to do research in Portugal and develop myself further in structural glycobiology, I returned to Portugal end 2009 and joined the protein crystallography group of Prof. Maria João Romão at FCT-NOVA (http://sites.fct.unl.pt/xtal/pages/members).  Here I implemented the glycan microarray technology combined with X-Ray crystallography to study endogenous lectin recognition systems (e.g. malectin, Dectin-1) and microbial glycan degradation of complex polysaccharides (bacterial cellulossomes). In 2013, I was awarded a 5-year Starting Grant under the highly competitive FCT Investigator international call, which allowed me to start my independent journey as a group leader and set-up the GlycoLAb – Functional Glycobiology Laboratory. As PI at FCT-NOVA, I have set-up a glycan microarray laboratory, supported by two research project grants from Portuguese FCT.

Since 2010, I have been enrolled in teaching Biochemistry and Metabolism at the Biochemistry Section of the Department of Chemistry at FCT-NOVA. I have also started teaching and training in Glycosciences to Master and Doctoral Programs within our Faculty and across Faculties and I am also actively participating in the e-learning course Glycobiology and Glycochemistry (http://www.fcm.citi-learning.info/moodle/course/view.php?id=2). In the future, I hope to implement the Glycosciences discipline in the undergraduate and postgraduate teaching programs of the Chemistry and Life Sciences Departments at FCT-NOVA. 

Research Focus

Glycans are present in all living cells and organisms, and their crucial roles and functions are as diverse as: acting as structural components for cell integrity or in regulating physiological and pathological processes, e.g., signalling, cell-cell communication, immune-recognition, host-pathogen interactions, protein folding and quality control). Although it is recognised by the scientific community that glycans represent a largely undiscovered resource for biological functions as well as for novel therapeutic opportunities, their study and the study of glycan-binding proteins has been hampered by several challenges. Among these are the following: 1) glycans have highly heterogeneous sequences; 2) are difficult to isolate from natural sources in sufficient amounts for characterization by conventional methods, and 3) the glycan-protein interaction is in general of low affinity. But these studies are being revolutionised by the advent of the highly sensitive and miniaturised glycan microarray technology, whereby sequence-defined glycan probes are robotically printed on solid supports as microspots (enclosed Figure). Glycan microarrays have proven to be powerful high-throughput screening tools for discovering glycan ligands and their function and evaluating specificities of glycan-binding proteins; also for assignment of functional glycan ligands in pathogen-host interactions. 

Despite the great advances in the glycan microarray field, its continuous development is essential, for example for studies of microbe-host interactions or to target specific mammalian or microbial glycomes. As the desired glycans that are relevant in those particular biological contexts are unavailable, it is critical to generate microarrays from biologically relevant ligand-bearing glycoconjugates, in order to reveal the oligosaccharide ligands they harbour, so that these can be isolated and characterised. This is the concept of our designer microarray approach. 

The focus of my research is on developing glycome-based designer glycan microarrays for interrogating glycomes and proteomes leading to: 1) glycan ligand discovery and function; and 2) unraveling of glycan-recogniton systems. These are applied to study endogenous and microbial glycan recognition systems and glycan-mediated pathogen-host interactions. I am following structure-function integrative approaches combining glycan-microarrays with complementary methodologies such as X-Ray crystallography, NMR and other biophysical techniques such as ITC, to characterize the interaction.  

Selected Publications

*Corresponding author; ¶Joint-first author; (#) number of citations in Scopus

- Liu Y, McBride R, Stoll M, Palma AS et al., The Minimum Information Required for a Glycomics Experiment (MIRAGE) project: improving the standards for reporting glycan microarray-based data, Glycobiology, ISSN:1460-2423

-Zhang H, Palma AS*, Zhang Y, Childs RA, Liu Y, Mitchell DA, Guidolin LS, Weigel W, Mulloy B, Ciocchini AE, Feizi T, Chai W Generation and characterization of β1,2-gluco-oligosaccharide probes from Brucella abortus cyclic β-glucan and their recognition by C-type lectins of the immune system. Glycobiology. 2016 Apr 6. [Epub ahead of print]

- Palma, A.S.*, Liu, Y., Zhang, H., Zhang, Y.,   McCleary ,B.V., Yu, G., Huange, Q.,  Guidolinf, L.S., Ciocchini, A.E., Torosantucci, A., Wang, D., Carvalho, A.L., Fontes, C.M.G.A. , Mulloy, B., Childs, R.A., Feizi, T., and Chai, W. (2015) “Unravelling glucan recognition systems by glycome microarrays  using the ‘designer’ approach and mass spectrometry”. Mol Cell Proteomics, 14: 974-88

- Suits, M.D., Pluvinage, B., Law, A., Liu, Y., Palma, A.S., Chai, W., Feizi, T., Boraston, A.B. "Conformational Analysis of the Streptococcus pneumoniae Hyaluronate Lyase and Characterization of Its Hyaluronan-specific Carbohydrate-binding Module".J Biol Chem. 2014 Sep 26;289(39):27264-77

- Gao, C., Liu, Y., Zhang, H., Zhang, Y., Fukuda, M.N., Palma, A.S., Kozak, R.P., Childs, R.A., Nonaka, M., Li, Z., Siegel, D.L., Hanfland, P., Peehl, D.M., Chai, W., Greene, M.I., Feizi ,T."Carbohydrate sequence of the prostate cancer-associated antigen F77 assigned by a mucin O-glycome designer array. J Biol Chem. 2014 Jun 6;289(23):16462-77 (#3)

- Neu, U., Mahmood Khan, Z., Schuch, B., Palma, A.S., Liu, Y., Pawlita, M., Feizi, T., Stehle, T. “Structures of B-Lymphotropic Polyomavirus VP1 in complex with oligosaccharide ligands” PLoS Pathog 9:e1003714, 2013.

- Crusat, M1., Liu, J1., Palma, A.S., Childs, R.A1., Liu, Y1., et al. Changes in the hemagglutinin of H5N1 viruses during human infection - Influence on receptor binding. Virology, 447: 326-337,  2013  (1co-first authors) (#8)

- Palma, A.S., Liu, Y., Childs, R.A., Herbert, C., Wang, D, Chai, W, Feizi, T. “The human epithelial carcinoma antigen recognized by monoclonal antibody AE3 is expressed on a sulfoglycolipid in addition to neoplastic mucins” Biochem Biophys Res Commun. 408:548-52, 2011 (#6)

- Neu, U., Maginnis, M.S., Palma, A.S., Stroeh, L.J., Nelson, C.D., Feizi,T., Atwood, W.J., Stehle, T.. Structure-function analysis of the human JC polyomavirus establishes the LSTc pentasaccharide as a functional receptor motif. Cell Host & Microbe 8:309-19, 2010 (#49)

- Childs R.A1., Palma, A.S. et al. “Receptor-binding specificity of pandemic influenza A (H1N1) 2009 virus determined by carbohydrate microarray” Nat Biotechnol. 27:797-9, 2009  (1co-first authors) (#158)

- Torosantucci, A., Chiani, P., Bromuro, C., De Bernardis, F., Palma, A.S., et al. “Protection by anti-β-Glucan Antibodies is associated with restricted β-1,3 glucan binding specificity and inhibition of fungal growth and adherence” PLoS ONE 4, e5392, 2009 (#66)

- Schallus, T., Jaeckh, C., Féeher, K., Palma, A.S., et al. “Malectin - a novel carbohydrate-binding protein of the endoplasmic reticulum and a new player in the early steps of protein N-glycosylation” Mol Biol Cell 19: 3404-3414, 2008 (#71)

- Palma, A.S., Feizi, T., Zhang, Y., Stoll, M.S., Lawson, A.M., Díaz-Rodríguez, E., Campanero-Rhodes, M.A., Costa, J., Gordon, S., Brown, G.D. and Chai, W. “Ligands for the beta-glucan receptor, dectin-1, assigned using ‘designer’ microarrays of oligosaccharide probes (neoglycolipids) generated from glucan polysaccharides”. J Biol Chem 281: 5771-5779, 2006 (#170).

Reviews

- Palma, A.S.*, Feizi, T., Childs, R.A, Chai, W. and Liu, Y. “The neoglycolipid (NGL)-based oligosaccharide microarray system poised to decipher the meta-glycome”. Curr Opin Chem Biol, 18, 87-94, 2014.

- Liu, Y., Palma, A.S., Feizi, T. “Carbohydrate microarrays: key developments in glycobiology” Biol Chem 390, 647-56, 2009 (#79)

Chapters in Books

- Palma, A.S*., Zhang, Y., Childs, R.A., Campanero-Rhodes, M.A., Liu, Y., Feizi, T., Chai, W. Yann Chevolot (ed.), Carbohydrate Microarrays: Methods and Protocols, Methods in Molecular Biology, Volume 808, Chapter 23:337-59, 2012

- Liu, Y., Childs, R.A., Palma, A.S., Campanero-Rhodes, M.A., Stoll, M.S., Chai, W., Feizi, T. “Neoglycolipid-Based Oligosaccharide Microarray System: Preparation of NGLs and Their Noncovalent Immobilization on Nitrocellulose-Coated Glass Slides for Microarray Analyses”. Yann Chevolot (ed.), Carbohydrate Microarrays: Methods and Protocols, Methods in Molecular Biology, Volume 808, Chapter 8:117-36, 2012

- Palma, A.S., Liu, Y., Muhle-Goll, C., Butters, T.D., Zhang, Y., Childs, R., Chai, W., Feizi, T. Methods in Enzymology, Elsevier Inc. Volume 478, Chapter 13: 265-86, 2010