Can we fill the missing link in the field of life science? The Human Glycome Atlas Project (HGA) will officially start its activities from April. The project seeks to make major advances in life science and medicine by comprehensively analyzing sugar chains, which are the third chain of life alongside the chains of nucleic acids that make up genomic DNA and the chains of amino acids that make up proteins, which cannot be explained by central dogma. The project was adopted for the first time in the field of life sciences by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) as a large‐scale academic frontiers promotion project. It is an all‐Japan initiative led by the Institute for Glyco‐core Research (iGCORE), Nagoya University and Gifu University, Tokai National Higher Education and Research System, the Exploratory Research Center on Life and Living Systems (ExCELLS), the National Institutes of Natural Sciences, and the Glycan and Life Systems Integration Center (GaLSIC), Soka University Project representative Kenji Kadomatsu, director of iGCORE, explained, "Glycan research is a field in which Japan has been a driving force. This pioneering project will lead the world."
Glycans are known for defining ABO blood types, but they are also very important as drug discovery targets. For example, in order for influenza viruses that have multiplied inside a cell to exit, the sugar chains on the cell surface need to be cleaved by neuraminidase, but Tamiflu has a very high therapeutic effect by inhibiting this cleavage. Research related to glycans has also led to several Nobel Prizes in chemistry, including one for Dr. Caroline Bertozzi.
However, the analysis of glycans is not easy. Glycans consist of about 20 different monosaccharides, in various combinations, of various lengths and with various branching patterns, so that, for example, there are a trillion combinations of just six monosaccharides linked together. However, there are probably several hundred million of them that have some function. The difficulty of analyzing them was a hurdle for life science researchers to participate in glycan research, despite Japan's leadership in this field.
"I was the head of the new academic field 'Neuroglycobiology' more than 10 years ago, where I poured my heart and soul into the fusion of two fields that had never intersected before: nerves and sugar chains," said Kadomatsu. "During that time, I was keenly aware of the solitary or isolated position of glycans and the importance of multidisciplinary fusion research. The HGA is an infrastructure project for the future of life sciences. It pushes the previously scarce information on glycans to the level of the other two chains present in life, the genome and proteins. This will enable researchers in all areas of life sciences, including neurology, cancer, genomics and proteins, to use glycan information for their own research without hesitation."
The research plan for the large‐scale academic frontier approved by MEXT covers a 10‐year period starting in 2023. The required costs will be approximately 32.1 billion yen.
In order to establish an information base, the HGA will first identify the shape of glycans in the human body and create a glycan precision map, which will form the basis for determining glycan structures. In addition, the HGA will conduct a comprehensive analysis of 20,000 blood samples in its first five years to learn the relationship between diseases and glycans in the field of dementia and ageing. That number will be increased to 200,000 samples in the second five years. Furthermore, the project will establish the basis for freely modifying glycans by obtaining information on all the enzymes (200 types) that make glycans in human cells, identifying the mechanism by which glycans are formed and constructing a glycan biosynthesis atlas.
By associating the glycan information analysis data obtained from this information base with disease‐related data containing glycan information, HGA will construct TOHSA, a glycan knowledge base that can be used by people worldwide.
The project will also build a rapid glycoproteomics automated system that enables the entire process from biological samples to sugar chain preparation, liquid chromatography separation, mass spectrometry and analysis in a single step. A system will be built to enable glycan structure analysis, which has been regarded as the most challenging task so far, to be performed homogeneously and in a short time by anyone, anywhere at any time. Digital transformation in the Lab will be realized by combining this with robots that automate experiments. Kadomatsu added, "In the future, we would like to build something on a scale that can be installed in hospital testing centers."
Various joint research projects on glycans will also be conducted in the research building completed in January this year at iGCORE and in the open mix laboratory set up at ExCELLS. GaLSIC develops analysis methods and will conduct the actual analysis of enormous amounts of data.
So, what kind of research will be carried out in the HGA?
Research will include dementia diagnosis, for example. Currently, blood proteins, genomics, imaging and cognitive function tests allow early diagnosis of mild cognitive impairment in the early stages before dementia, but improving cognitive function is not easy. Therefore, by analyzing the glycan structure from a large cohort of samples, combined with clinical data and clinical assessment, it will be possible to predict the risk of developing mild cognitive impairment more than 10 years before it occurs.
The HGA is a cohort study based on large‐scale and comprehensive glycan structure analysis and is a project in which Japan has an advantage in analysis and other technologies. However, if a certain technical information management system is not established, there is a possibility that other countries will outperform Japan as in other cases in the past. At the same time, international cooperation is also important and requires strategic management. This will require a certain scale of budget investment from the outset.
This article has been translated by JST with permission from The Science News Ltd. (https://sci-news.co.jp/). Unauthorized reproduction of the article and photographs is prohibited.