Laboratories and faculty

Microbial Interaction

Assoc prof. Watanabe Assoc prof. Kimata
Associate Professor
WATANABE Daisuke mailアイコン
KIMATA Yukio mailアイコン
Assistant Professor
NISHIMURA Akira mailアイコン
MOROZUMI Yuichi mailアイコン
NAKASE Yukiko mailアイコン
Labs HP

Outline of Research and Education

How do microorganisms behave and interact to build complex ecosystems? We study yeasts and other unicellular organisms familiar to humans at the molecular, metabolic, cellular, and ecological levels to deepen understanding of diversity in the microscopic world. Our achievement will also contribute to modern biotechnology in food and health science (Fig. 1).

Major Research Topics

Microbial ecology in food fermentation (Fig.2)

The yeast Saccharomyces cerevisiae is an important eukaryotic microorganism indispensable for the production of fermented foods, such as bread and alcoholic beverages. Traditionally, most studies of yeast have been done by pure culture in simple media. However, in order to understand the true ecology of yeast, it is necessary to clarify its behavior in a complex system in which diverse components and microorganisms are mixed together, as in the case of food fermentation. In this laboratory, we challenge to elucidate the molecular mechanisms of the interactions between yeast, other fermenting microorganisms (e.g., lactic acid bacteria), and ingredients (e.g., grains and fruits), using a unique environment inspired by the actual production process of fermented foods.

Enforcement/enlargement of the endoplasmic reticulum (Fig.3)

The endoplasmic reticulum (ER) is an organelle in which secretory proteins and lipidic molecules are biosynthesized. Dysfunction or functional shortage of the ER is cumulatively called ER stress and provoked, for instance, in pancreatic islets, which secrete abundantly proteinous hormones. To cope with ER stress, eukaryotic cells commonly trigger the ER stress response, which is a gene-expression program leading to enforcement and enlargement of the ER. Using yeasts as a model organism, we are approaching the molecular mechanism of the ER stress response. Moreover, we have generated yeast cells in which the ER stress response is artificially and constitutively induced even without external stress stimuli. They have enforced and expanded ER, from which beneficial secretory proteins (such as human antibodies and proteinous hormones) and functional lipidic molecules are abundantly synthesized.

Metabolic regulations of functional amino acids and their applications in yeast (Fig. 4)

Amino acids are proteinogenic compounds that organisms additionally exploit as aroma precursors and stress protectants. Therefore, the control of amino acid content is expected to contribute to adding to the value of fermented foods and alcoholic beverages. We have constructed yeast strains with high functionality focused on the metabolic regulatory mechanisms and physiological roles of functional amino acids (proline, arginine, leucine, cysteine, etc.) found in yeast.

TOR (Target Of Rapamycin) signaling pathway (Fig. 5)

The target of rapamycin (TOR) kinase forms two distinct multi-subunit complexes termed TORC1 and TORC2 to regulate cellular growth and proliferation in response to diverse stimuli, such as nutrients and growth factors. Deregulation of TOR signaling is often associated with human diseases, including cancers, diabetes, and neurodegenerative disorders, and therefore, comprehensive understanding of TOR pathway is critical to develop informed strategies to treat the diseases. We have established a model system in S. pombe to discover molecular mechanisms that control TORC1 and TORC2.

Fig. 1 Internal and external interactions of the cell.
Fig. 2 How to understand the true ecology of yeast.
Fig. 3 Expansion of the ER by artificial ER stress response.
Fig. 4 Metabolic regulation of functional amino acids and their applications in yeast.
Fig. 5 TOR signaling pathway stimulated by nutrients and insulin/growth factors.


  1. Watanabe et al., Res. Sq. (preprint), DOI: 10.21203/, 2023
  2. Watanabe and Hashimoto, Res. Sq. (preprint), DOI: 10.21203/, 2023
  3. Nguyen et al., Appl. Environ. Microbiol., 88, e01083-22, 2022
  4. Ishiwata-Kimata et al., Front. Cell Dev. Biol., 9, 743018, 2022
  5. Isogai et al., Appl. Environ. Microbiol., 88, e02130-21, 2022
  6. Nishimura et al., Microorganisms, 9, 1902, 2021
  7. Morozumi et al., J. Cell. Sci., 134, jcs258865, 2021
  8. Fukuda et al., eLife, 10, e60969, 2021