Dublin-Oxford Gycobiology Group



Group Details

The Dublin-Oxford Lab includes 16 PostDocs, 3 Research Assistants and 1 PhD student. The groups academic and industrial research programs is split into several sections including technology development, cancer and disease research, bioinformatics, immunology and training.

A brief description of each group member is available below, click the name to see details.



PostDocs

Giorgio Carta

Eoin Cosgrave

As a postdoctoral researcher with NIBRT, my project is directed towards the development of an Fc receptor (FcR) platform designed to assess the biological activity and efficacy of antibody-based therapeutics. It is now appreciated that the N-linked glycan located on Asn-297 of each Cγ2 domain of the two IgG heavy chains play an important role in co-ordinating immune effector functions such as antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). These effector functions are mediated through interaction with specific receptors of the immune system, including the Fcγ receptor family (FcγRIa, FcγRIIa/b, and FcγRIIIa/b) and complement receptors MBL and C1q, which bind to the Fc region of IgG. The Fc-FcR interaction is a critical aspect of immunology as it links antigen recognition to antigen clearance. Our aim is to assess how changes in IgG glycosylation at Asn-297 influence its interaction with Fc receptors and what impact this has on the associated biological activity. The ability to engage specific Fc receptors has been of significant importance to the members of the biopharmaceutical industry intent on providing antibody-based therapies with a capacity of enhancing ADCC for the treatment of cancer.

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Eugene Dempsey

Chronic inflammation has long been understood to be a hallmark of cancer development. In the last decade some of the underlying mechanisms linking inflammation and cancer have begun to be unravelled, however, many of the processes are still poorly understood. Glycosylation is an enzymatic process whereby saccarides are added to proteins, lipids or other organic molecules, often giving rise to quite large and complex structures. The glycosylation of proteins is crucial for their correct folding but can also alter their function and stability.

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Margaret Doherty

My role within NIBRT is to further advance our current high-throughput technology and develop a fully automated system utilizing a robotic platform. Current analytical approaches to obtaining detailed product quality data require extensive sample preparation (e.g. to release and label glycans) and analysis (e.g., HPLC or CE-LIF, LC-MS peptide mapping), which delay the generation of key information. The ability to obtain rapid information, particularly regarding glycoform structures on-line would greatly enhance process development and optimization. Ultimately the robotic platform will be interfaced directly with processing operations to enable monitoring of cell culture conditions and the acquisition of real-time information to ensure optimized product quality. Other aspects of my post include development and optimization of methodologies for O-glycan release and analysis, N-glycan analysis, beta testing of innovative products to facilitate glycan analysis, development of proprietary databases for IgG analysis and technology transfer.

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Rebecca Duke

I am a Postdocotoral Researcher with NIBRT, where my work involves the discovery and characterisation of novel enzymes (O-glycanases and exoglycosidases) for the cleavage of O-glycans from proteins, and their subsequent sequencing. As O-glycans are involved in many aspects of biology, these enzymes are of fundamental and commercial value. This project utilises a combination of technologies, such as the use of metagenomic-libraries, robotics-based screening strategies, HPLC-based glycoanalytical methods and enzyme-based investigations.

My research background is in Supramolecular Chemistry, where my PhD thesis detailed the synthesis and spectroscopic investigations of novel colorimetric and fluorescent sensors for anions. Before coming to NIBRT, I spent some time in the veterinary pharmaceutical industry.

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Mark Hilliard

Karina Marino

The Glycoscience Research Cluster (GRC) brings together Ireland’s growing body of expertise in this subject; it focuses on deciphering and exploiting the role of host mucosal glycans on the microbial ecology of the gut.

My role in this program is to analyze alterations in epithelial cell and mucin glycosylation in the colonisation/infection model of a mucosal surface. Therefore, it will be of fundamental relevance to understanding glycan-driven mechanisms in mucosal defence. Methods for isolation and analysis of mucin glycosylation using HPLC and MS will be improved and applied to the samples generated. Furthermore, this glycosylation analysis will not only provide structural data on relevant oligosaccharides, but will also indicate relative activities of glycosyltransferases and other glycosylation determining enzymes.

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Niaobh O'Donoghue

I have been employed with NIBRT since October 2007. My role in NIBRT is to manage the Dublin-Oxford Glycobiology Laboratory, headed by Prof. Pauline M. Rudd and to manage NIBRT’s custom Analytical Glycobiology Services for the worldwide scientific and biopharmaceutical industries.

My research background is in Clinical Pharmacology where I specialised in proteomics and mass spectrometry as tools for research in this field. My PhD thesis was entitled the Proteomic Analysis of the Platelet Pharmacological Response. I have had the opportunity over the past number of years to work with diverse research groups utilising mass spectrometry as a tool to assist them with answering their biological questions.

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Oscar Potter

As a postdoctoral researcher in glycoananalytical chemistry at NIBRT, I am responsible for the development of multidimensional nano-liquid chromatography-mass spectrometry systems for comprehensive analysis of released oligosaccharides. This project is collaboration with the developers of the Agilent HPLC-Chip Mass Spectrometry system in Santa Clara, California. Funding and instrumentation for the project are provided through an Agilent Thought Leader Award that was presented to Pauline Rudd in May 2010.

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John O'Rourke

 

Radka Saldova-Fahey

I joined the Glycobiology group in May 2005 as a Research Assistant, defended my PhD in Institute of Chemical Technology Prague in November 2007 and continue as a Postdoctoral Research Assistant. My main research interest is focused on cancer. I am currently working on various glycosylation based approaches to find biomarkers for cancer. The main techniques that I have applied in my project are N-glycan release from whole serum glycoproteins of cancer patients and controls followed by glycan sequencing using HPLC and exoglycosidase digestions. Preeliminary results from the glycan analysis have led to electrophoresis- 1D and 2D gels, immunochemical methods and protein purification techniques. I am also now applying these techniques together with epigenetics analyses with the ovarian cell line OVCAR3, to further understand the glycosylation changes contributed by the tumour. I am also analyzing glycosylation in mouse inflammation model to understand role of inflammation in cancer and its effect on glycosylation.

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Michael Schomberg

My current research interests lie on the development of high-throughput methods for the analysis of antibody N-glycans. The techniques involved in my research include the development and optimisation of RP-HPLC based methods for glycan analysis and the characterisation of glycans by mass spectrometry.

During my scientific education I particularly acquired skills and experiences in the fields of HPLC, mass spectrometry, CE and cell culture bioprocessing.

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Weston Struwe

I am a Postdoctoral Research Fellow with NIBRT in the field of carbohydrate mass spectrometry, namely N- and O-linked glycans. Our current approach utilizes both negative mode MS/MS analysis pioneered by our research colleague Dr. David Harvey from Oxford University as well as sequential MS, or MSn, analysis following permethylation. This twofold approach enables the comprehensive analysis of glycans, whereby detection of structural isomers, resolving linkages between residues and determining the level of branching in a given composition is achievable. We currently employ a Waters-Micromass Q-Tof Ultima Global mass spectrometer for negative mode MS/MS analysis and an Agilent 6340 Ion Trap instrument for MSn of permethylated structures.

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Jayne Telford

Post-doctoral researcher. My research involves analysing serum samples from controls and from schizophrenic patients in order to identify alterations in glycosylation patterns. My project is in collaboration with laboratories in Cambridge, UK and Germany and the overall aim of the research is to develop minimally invasive, high throughput, low cost molecular assays for the early diagnosis of schizophrenia.

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Tharmala Tharmalingam

I am a Postdoctoral researcher working on the glycomics section of the Reproductive Biology Research Cluster which brings together researchers across many disciplines but focusing on the fertility of domestic animals using a variety of technologies including established animal models, in vitro tissue culture and bioinformatic tools for the analysis of reproductive tissues (follicles, oocytes, embryos, uterus, cervix).

In particular my project looks at the variability of N- and O- linked glycosylation of the cervical mucus throughout the oestrous cycle of cattle.

My Ph.D. research interests included the optimization of recombinant protein production (IFN-beta and tPA) from CHO cells using high density cultures obtained by utilization of microcarriers. The projects involved the production of the protein, quantification of the protein, and analysis of the glycosylation to ensure product quality.

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Research Assistants

Barbara Adamczyk

I graduated with a degree in Biotechnology from the department of Life Sciences at Poznan University in 2009. I completed a MSc. thesis in the Laboratory of Developmental Genetics at the Institute of Human Genetics, the aim of the study was to screen for mutations in a highly conserved VASA gene among infertile men to evaluate significance of VASA alterations for male infertility. During my studies I spent half a year on Socrates fellowship in Spain collaborating with Center for the conservation and breeding of the agrodiversity in Valencia and developing my interests of molecular biology. Participation in programme for students Work and Travel in USA during summer time 2006 and 2007 allowed me to gain experience in industrial quality assurance.

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Patrick Jennings

I joined NIBRT as a research assistant in August 2010. My main focus will be the detailed N-linked glycan analysis of biotherapeutics and glycoproteins for biotech companies, regulatory bodies and academic institutes. I will also be involved the set up and operation of the new NIBRT building- writing standard operations procedures, health and safety, training etc.

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Joanne Withers

I graduated in 2006 from the University of Southampton with a BSc Biochemistry degree and joined NIBRT in October 2010 as a Research Assistant. My role is to perform N-linked glycan analysis for contract research using HPLC and exoglycosidase digestions.

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PhD Student

Marie Galligan

My bachelor’s degree is in Mathematical Sciences and Computing, with an emphasis on statistics in the final two years.

My area of interest is biostatistics, the subject for which i’m hoping to obtain a PhD. I’m currently working with Prof. Thomas Brendan Murphy to develop novel techniques for the analysis of Glycomics data, generated by Pauline Rudd’s research group, to aid in the diagnosis and prognosis of different diseases and also to identify glcan biomarkers for these diseases.

An appropriate statistical model for this data needs to take into account that the data are relative, as opposed to absolute, quantities. Such data is referred to as compositional. There have been various methods developed to overcome the difficulties in the analysis of compositional data, but the research in this area is not extensive. I’m currently attempting to fit nested Dirichlet models to the data, which might then be used for classification purposes.

My PhD funding comes from IRCSET, under the program for Structured PhDs in Bioinformatics and Computational Biomedicine.