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
MOROZUMI Yuichi mailアイコン
NAKASE Yukiko mailアイコン
AKASAKA Naoki mailアイコン
Labs HP
https://bsw3.naist.jp/microbial_interaction/en/top/

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 Aspergillus oryzae), and ingredients (e.g., grains and fruits), using a unique environment inspired by the actual production process of fermented foods. Recently, we have made a series of new discoveries about the signaling pathways controlling alcohol fermentation in yeast, about yeast and lactic acid bacteria that play a central role in the production of naraduke (Japanese traditional pickles), and about plant resident microorganisms that may hold the key to the origin 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. Another intriguing topic concerning the yeast strains with constitutive and artificial induction of ER stress response is that they may be highly tolerant to stress stimuli, which is beneficial for ethanol fermentation by yeasts.

TOR (Target of Rapamycin) signaling pathway (Fig. 4)

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 the fission yeast S. pombe to discover molecular mechanisms that control TORC1 and TORC2. We have recently discovered that TORC1, a well-established growth promoter, negatively regulates growth of fission yeast cells at high temperatures.

fig.1
Fig. 1 Various interactions in microbial ecosystem.
fig.2
Fig. 2 How yeast regulates alcohol fermentation has remained a mystery, but our research using sake yeast has revealed a link to cell wall synthesis (1). We also recently focus on the microbiome of naraduke pickles, a typical traditional fermented food (2), and on the origins of fermented foods described in ancient texts (3).
fig.3
Fig. 3 [Left panels] The ER was illuminated by expression of a fluorescent protein-tagged ER-marker protein. By constitutive induction of the ER response, the ER was highly expanded. [Right panels] Carotenoids was produced in yeast cells by introducing heterologous carotenoid biosynthesis genes. By constitutive induction of the ER response, cells exhibited more abundant carotenoid production.
fig.4
Fig. 4 TOR signaling pathway stimulated by nutrients and insulin/growth factors (i). We have demonstrated that the TOS motif represents an evolutionarily conserved mechanism of the substrate recognition by TORC1 (ii). We have recently focused on the growth regulation of fission yeast cells at high temperatures (iii).

References

  1. Morozumi et al., iScience, 27, 108777, 2024
  2. Watanabe et al., Int. J. Mol. Sci., 25, 304, 2024
  3. Tai et al., Mol. Cell Biol., 43, 675-692. 2023
  4. Watanabe et al., NPJ Sci. Food, 7, 37, 2023
  5. Fauzee et al., Front Microbiol., 14, 1157146, 2023
  6. Watanabe and Hashimoto, Sci. Rep., 13, 9279, 2023
  7. Nguyen et al., Appl. Environ. Microbiol., 88, e01083-22, 2022
  8. Ishiwata-Kimata et al., Front. Cell Dev. Biol., 9, 743018, 2022
  9. Morozumi et al., J. Cell. Sci., 134, jcs258865, 2021