For candidate

The purpose of our research is to elucidate the role of glycans in living organisms. In Drosophila melanogaster, ES cells, iPS cells, and cancer cells, we are clarifying glycan functions by regulating the expression of glycan-related genes using various genetic engineering techniques. In addition, for some genes, knockout mice are created and analyzed. Recently, we have also begun analysis of inherited diseases caused by glycan deficiency. The research theme of each student will be selected from the ones related to (1)-(3) below. All of these required the knowledge of developmental biology, stem cell biology, cell biology, biochemistry, and molecular biology.

(1) Analysis of glycan-related genes using Drosophila mutants and RNAi files; Elucidation of the roles of glycans conserved across species.

Drosophila melanogaster is one of the most useful model organisms. Focusing on “the roles of glycans conserved across species”, we are analyzing the functions of glycan-related genes in Drosophila melanogaster. By the phenotypic analysis of knockdown flies and mutants and biochemical and molecular biological analyses, we clarify the role of glycans in the development of organisms. Now, we analyze the glycan structure and the mechanism for (A) maintenance and differentiation of hematopoietic stem cells and (B) nerve axon compartmentalization that we found as the novel phenomenon.

(2) Elucidation of glycan function in mouse and human pluripotent stem cells (ES cells and iPS cells)

We investigate whether the glycan functions are common to humans and other organisms, by using cultured cells, mainly ES cells. Specifically, the objective is to elucidate “the role of glycans in maintaining undifferentiated stem cells and their differentiation”. In 2008, this project for the first time revealed that “glycans are involved in the maintenance of ES cells”. To date, it has been clarified that (1) heparan sulfate, (2) LacdiNac structure, and (3) O-GlcNAc structure are required for maintenance of naïve mouse ES cells. Then, we perform analysis of glycans involved in the regulation of different states of stem cells, such as the two different stages of development of pluripotent stem cells (naïve state and prime state).

(3) Functional analysis of PAPS transporter knockout mouse

The PAPS transporter is essential for sulfation of glycans and proteins, and without it, each molecule cannot undergo sulfation modification. We first isolated and identified this gene in 2003. We are currently making knockout mice and analyzing the function of sulfated glycans in various abnormalities found in the knockout mouse.