For Prof. Pauline Rudd, it all began with alchemy. "When I was about 10, we visited my uncle, who's a physicist,” she recalled. “And he had a book on alchemy. Don’t ask me why, but something in it really inspired me. I think it was the idea of changing one thing into another."
Prof. Rudd has been changing one thing into another ever since. Supported by academic funding from the EU and from Ireland, she has developed strategies for changing glycans into clinical markers in the diagnosis and treatment of cancers. An invited review of her published findings on glycans as biomarkers, co-authored with Barbara Adamczyk and Tharmala Tharmalingam, was recently published by the scientific journal Biochimica et Biophysica Acta. This research may one day lead to the development of simple blood tests to diagnose cancers and measure the impact of treatments.
Understanding how human disease can change complex glycan processing pathways has been very important for her work with pharmaceutical companies at The National Institute for Bioprocessing Research and Training (NIBRT) in Dublin, Ireland, where she is a Principal Investigator and an Adjunct Professor at University College, Dublin. “We now have many clues about where problems might arise during the bioprocessing of glycosylated therapeutics, such as monoclonal antibodies and erythropoietin. The need for stringent, quantitative glycan analysis has driven our technology development”, says Prof. Rudd.
In a collaboration with Waters, Prof. Rudd's research team at NIBRT also developed GlycoBase 3+, the world’s first database for glycan analysis by UltraPerformance Liquid Chromatography® (UPLC®). A repository of chromatographic retention positions expressed in glucose units for sets of glycan structures associated with a range of biotherapeutics, the GlycoBase 3+ Database gives biopharmaceutical manufacturers a fast and powerful tool for confirming the structure of various glycosylated proteins. When used during the manufacturing process, GlycoBase 3+ enables biopharmaceutical manufacturers to gain greater control over their manufacturing process, thereby ensuring safety, efficacy and regulatory compliance. NIBRT and Waters are co-marketing the database worldwide.
Waters liquid chromatography (LC) and mass spectrometry (MS) technologies have been integral to Prof. Rudd's work since the early 1990's when she discovered that using a Waters HPLC system coupled with exoglycosidase array digestions of whole pools of glycans could reduce the time required to separate and analyze glycans from months to just a couple of days. Today, in some cases, the time from sampling to analysis has dropped dramatically to just a few hours. According to Prof. Rudd, the high throughput and reproducible nature of Waters' ACQUITY UPLC platform is helping to further the rapid, detailed analysis needed for bioprocessing as well the integration of glycomics with other fields, such as proteomics and genomics, thereby making systems glycobiology a reality in both bioprocessing and natural systems. A recent review in Nature Chemical Biology, with co-authors Karina Mariño, Jonathan Bones and Jayesh Kattla, emphasizes the importance of orthogonal technologies for full glycan analysis “and for defining the question in order to find a path through the maze.”
“I’m very fond of telling my students that technology, applications and biology really go hand in hand,” she explained, “because you can have the best idea in the world but if you haven’t got the technology to answer the question, it’s going to lie fallow until somehow the technology comes.”
A native of the New Forest, Lymington on England's south coast, Pauline Rudd earned her BSc in Chemistry at the University of London and a PhD in Glycobiology at the Open University, UK. A co-founder of Wessex Biochemicals (later Sigma London), Prof. Rudd was mostly recently a University Reader in Glycobiology and Senior Research Fellow in the Glycobiology Institute, Oxford, before relocating with the Institute's Glycan Sequencing Group to NIBRT in 2006. Dr. Rudd is also a Fellow of the Royal Society of Medicine, London, a Visiting Professor at St. George’s Hospital, London and an Adjunct Professor at Northeastern University, Boston.
Throughout her distinguished career, Prof. Rudd, a mother of four and grandmother of nine, has never lost the sense of wonder that first sparked it. As she said in a recent invited lecture at Cumberland Lodge in Windsor: “Many who embark on a life in science are both deeply passionate and deeply rational people. They have entwined and integrated two major strands of their personalities because neither aspect represents who they really are, and alone neither enables them to reach for the understanding of the creation that they long for.”
“It’s always mattered to me that science is not a materialistic pursuit,” said Prof. Rudd. “Many of the great scientific traditions of the past believed that you had to be true as a person too. If nature was going to reveal these things to you, you had to be worthy of it in a way. And I still feel that. It’s a huge privilege if you make a discovery. And there’s some sort of personal responsibility for using that wisely. That’s part of my life that really matters”