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Human Genetics

  • account_circleKimiko KobayashiPhD, Prof.
  • account_circleYuya OhharaPhD, Research Asst. Prof.
New approach for establishment of preventive method for lifestyle-related diseases
1. Interaction of genetic and environmental factors related to the development of lifestyle-related diseases

The prevalence of lifestyle-related diseases such as diabetes, hypertension, and obesity are continuously increasing in many countries. A combination of multiple genetics and environmental factors is considered to contribute to the pathogenesis of such diseases (Fig 1). With the recent progress of genome science, numerous susceptibility genes for lifestyle-related diseases have been identified. In our laboratory, we analyze a variety of interactions between such susceptibility genes and dietary nutrient intake to better understand how these interactions affect the development of lifestyle-related diseases. Furthermore, we use fruit fly, Drosophila melanogaster, to study in vivo function of disease-related genes. Drosophila is an excellent model organism because most of the disease-causing genes and functional physiological processes in Drosophila are conserved in human.

2. Elucidation of Genetic and Nutrient Cues Regulating Growth and Development

Nutrient and genetic signaling also has a central role in the progression of growth and development. For instance, nutrient-dependent signaling pathway, such as target of rapamycin (TOR) pathway, controls cell division, growth, and differentiation in cell autonomous manner, as well as systemic growth and maturation through the regulation of endocrine system (Fig 2). Our main interests are (1) how cell division, growth, and maturation are coordinately controlled in accordance with nutrient status; (2) how TOR pathway integrates nutrient status to determine the production of steroid hormone which terminates systemic growth period and induces systemic maturation. To address these issues, we have been using Drosophila, and performing genetic screen to identify novel regulators of growth and development. These studies provide the basis to understand the molecular mechanism regulating growth and development and its significance.

Figure 1
Nutrient and genetic cues affecting human health
Figure 2
TOR is essential for cell growth
(A and B) Control (A) and TOR-inhibited tissues
References
  1. Ohhara Y, Nakamura A, Kato Y, Yamakawa-Kobayashi K. Chaperonin TRiC/CCT supports mitotic exit and entry into endocycle in Drosophila. PLoS Genet. 15:e1008121 (2019).
  2. Yamakawa-Kobayashi K, Otagi E, Ohhara Y, Goda T, Kasezawa N, Kayashima Y. The Combined Effects of Genetic Variation in the CNDP1 and CNDP2 Genes and Dietary Carbohydrate and Carotene Intake on Obesity Risk. J Nutrigenet Nutrigenomics. 10:146-154 (2017).
  3. Ohhara Y., Kobayashi S., Yamanaka N. Nutrient-Dependent Endocycling in Steroidogenic Tissue Dictates Timing of Metamorphosis in Drosophila melanogaster. PLoS Genet. 13:e1006583 (2017).
  4. Ohhara Y, Shimada-Niwa Y, Niwa R, Kayashima Y, Hayashi Y, Akagi K, Ueda H, Yamakawa-Kobayashi K, Kobayashi S. Autocrine regulation of ecdysone synthesis by beta3-octopamine receptor in the prothoracic gland is essential for Drosophila metamorphosis. Proc Natl Acad Sci USA. 112:1452-7 (2015).
  5. Goda N, Murase H, Kasezawa N, Goda T, Yamakawa-Kobayashi K. Polymorphism in microRNA-binding site in HNF1B influences the susceptibility of type 2 diabetes mellitus: a population based case-control study. BMC Med Genet. 16:75 (2015).