Jump to content
Powered by

Breakthrough for glycomics

New databases and bioinformatic tools provide the field of glycomics with a solid basis for dynamic development in molecular biology and medicine. Willi von der Lieth, a researcher from Heidelberg, was an important pioneer of glyco-bioinformatics. His sudden death is a great loss for this new scientific field.

Although the biological importance of glycosylation in development processes, cell-cell communication, immune reactions, disease and wound healing and many other cellular functions has been known for some time, glycobiology, the science which deals with the complex carbohydrates combined with proteins and lipids, in particular on the cell surface and secretion products, has not received as much attention.
"Glycoscience comes of age." Cartoon about the importance of glycosciences. (Photo: EMBO Reports)
Progress in this field of science has largely been made in isolation from mainstream molecular and cell-biological research and completely unnoticed by the general public. This lack of interest is also reflected by poor levels of research funding given to this discipline. While the sequencing of the human genome attracted between 50 and 150 million US dollars, total funding given to the glycosciences between 1993 and 2003 amounted most probably to less than 5 million dollars (K. Schmidt, New Scientist 176, 2002).

Complexity and wrong information

Unlike genomics, proteomics and transcriptomics, glycomics is fiendishly complex which may have led to its lack of appeal. Although only about 12 different monosaccharides are involved in the glycosylation processes that are important for humans, there are many ways they might be coupled to the carrier molecules. They can be coupled to different glycosylation sites in the proteins, be connected to long chains and have many branches, reaching an enormous size. Sequence, length and the degree of branching of the sugar chains all depend on numerous different factors and vary with regard to tissue type, cell metabolism, age and differentiation state of the organism.
Homology model of 5-lipoxygenase (Figure: University of Frankfurt/M. Organic Chemistry)
A major methodological obstacle in the analysis of the glycosylation patterns is the fact that they are not encoded in the DNA sequence as is the synthesis of nucleic acids and proteins. Although the enzymes, which synthesise the individual monosaccharides, are defined by the genome in the same way as the glycosyltransferases which add the monosaccharides to the glycan chains, their activity cannot be predicted.

A generally binding classification system, which groups glycans according to their biological functions, structural elements and diseases, is still missing. Experimental data such as MS spectra, HPLC profiles or NMR spectra are presented and grouped in different ways in expert journals; the inclusion of the data in databases is incomplete and, in some cases, incorrect. According to Lütteke and von der Lieth (BMC Bioinformatics 5, 2004), approximately 30 per cent of all glycoprotein data in the Protein Data Bank of the Research Collaboratory for Structural Bioinformatics are either wrong or very improbable.

New initiatives to develop glycomics further

Over the last few years, huge progress has been made and glycomics is gradually receiving the recognition it deserves. In both molecular and biological research it is of vital importance, for example in the physiological and pathological development of humans. As a result, the Consortium of Functional Glycomics (CFG) was established with the support of the US National Institute of General Medical Sciences in Bethesda, MD, USA. It has the objective to deepen the understanding of the function of carbohydrate-protein interactions on the cell surface and in cell-cell communication.
Screenshot of a softwaretool for protein analysis
GlycoWorkbench. A page of the Internet-based data bank EUROCarbDB. (Photo: www.eurocarbdb.org)
Bioinformatics plays an important role in these efforts, as well as in many other initiatives such as the multidisciplinary EuroGlycosciences Forum in Oxford, UK (www.glycosciences.org.uk). EuroCarbDB (www.eurocarbdb.org) has gained central importance. It is a platform of integrated carbohydrate databases and informatic tools that collects the huge amounts of information gained in the glycosciences and glycomics from a variety of sources and makes them available. The platform was created as part of the 6th European Research Programme.

Willi von der Lieth – pioneer of glyco-bioinformatics

Dr. Claus-Wilhelm von der Lieth, head of the work group “Molecular Modelling” in the Central Spectroscopy Department of the German Cancer Research Centre (DKFZ ) in Heidelberg, was the coordinator of EuroCarbDB and one of the leading scientists in this field.
Seven superimposed glycan fragments of the influenza neuraminidase (Photo: In silico Biology 2, 2002)
Following his PhD, von der Lieth accepted a position at the DKFZ in 1980, where he developed computer-assisted information systems for application in spectroscopy. Back in 1984, he introduced the methods of molecular modelling. After a period of research in Sweden, where he worked on the simulation of the molecular dynamics of peptides, von der Lieth returned to the DKFZ in 1987. His major research focus was computer-assisted three-dimensional, molecular structure models. He was a member and later chairman of the scientific computing advisory board at the DKFZ for many years and was active in numerous scientific associations and on the editorial board of the journal Carbohydrate Research. He published more than one hundred papers. Besides coordinating EuroCarbDB, von der Lieth was also the co-director of the ‘Human Disease Glycomincs/Proteome Initiative’ (HGPI/HUPO) and member of the US Consortium for Functional Glycomics (CFG). Colleagues who worked with him in EuroCarbDB said that “in the DKFZ it was largely unknown that Willi was regarded as a world-leading scientist and pioneer in the field of glycomics.”
Dr. Claus-Wilhelm von der Lieth (13.7.1949 - 16.11.2007) (Photo: DKFZ)

He had no interest in habilitating and becoming a professor, but always supported the academic career of his colleagues. His own research focused mainly on the field of clinical chemistry and medicine, in particular on cancer research. On the 16th November 2007, von der Lieth died of the disease he had investigated and fought against with unflagging energy and dedication over many decades. Rahul Raman, CFG Bioinformatic Core Director at the Massachusetts Institute of Technology said in the obituary published by EuroCarbDB: “Willi has inspired the evolution of the field of glyco-bioinformatics. He was a pioneering leader in the task of developing standardized glycan databases and bioinformatics tools for use in laboratories around the world. We will miss him tremendously.” 

Website address: https://www.gesundheitsindustrie-bw.de/en/article/news/breakthrough-for-glycomics