Advanced Systems-Biology: Designing The Biological Function | Global COE

Tsukasa MATSUDA

Affiliation /Position	Graduate School of Bioagricultural Sciences, Department of Applied Molecular Biosciences, Professor
Doctorate	Doctor of Agriculture, Doctor of Medical Science
Research interests	Control of biological functions for production and utilization of useful materials
address	tmatsuda＠agr.nagoya-u.ac.jp ※Replace full-width “＠” with half-width “@” when you send e-mail. +81-52-789-4129
	Laboratory

Outline of research

We have an interest in biological phenomena involving substantial changes in function and morphology. Our investigations are aimed at understanding the control of biological functions at the cellular and organ levels, and also to artificially control and make efficient use of them. Current projects are as follows:

・Differentiation and involution of mammary gland (cells) and synthesis and function of milk constituents.
The mammary gland is an organ unique to mammals. Mammary epithelial cells, which are parenchymatous cells of mammary gland, are able to produce and secrete substantial quantities of proteins, lipids and lactose; these cells undergo cell proliferation and differentiation during pregnancy. During the weaning period, the mammary gland quickly involutes to pre-pregnancy status; during subsequent pregnancies, the organ can repeat this cycle of proliferation, differentiation, and involution. We have been studying a wide range of aspects of milk production in dairy cattle, as well as infantile nutrition and maternal immunity in mammals including humans. Currently, we are studying the mechanism of mammary gland involution as well as characterizing non-immune protective factors contained in milk.

・Mechanism of egg-envelope formation in birds, and characterization of its functions in fertilization and early embryogenesis
The egg-envelope (“Zona Pellucida” in mammals) is an extracellular matrix that covers the ovum; this matrix plays important roles in growth of the ovum as well as in fertilization and early embryogenesis. Although birds are industrially important organisms, their egg-envelope is less well understood than that of other vertebrates. It seems that main reasons for the delay in understanding is that birds are oviparous and internally fertilized, and also because the egg yolk is large and hard to handle. Meanwhile, the system has distinctive merits for experimental study: it is easy to obtain large quantities of bird eggs, and suitable biochemical approaches have been developed. We have discovered that the net-like matrix structure of the egg-envelope is developed from an assembly of noncollagenous globular proteins. Studies of egg-envelope formation mechanism in the ovary and the mechanism of egg-envelope breakdown at the time of fertilization are underway in our lab.

・Synthesis and accumulation of proteins in plant seeds.
Plant seeds contain accumulated carbohydrates, lipids, and proteins necessary for germination and early growth. Cereal seeds, which contain high levels of nutritious components, are especially important food resources for human and livestock. However, some constituents of these seeds have negative influences on the health of humans or livestock who eat the grain. We are currently conducting studies aimed at reducing of the negative constituents, increasing the levels of nutritious constituents, and introduction of useful novel constituents into agricultural grains.

・Antibody uptake through gastrointestinal tract, and recognition and responses by the mucosal immune system.
For many years, it has been known that some pathogenic bacteria produce toxic proteins that must be taken up through the gastrointestinal tract in order to exert their toxicity in the body. Prions may also enter the body via a similar mechanism. Similarly, some proteins from ingested foods and drugs are also taken up into the body through the intestine. Protein antigens absorbed from the intestinal tract stimulate the mucosal immune system and induce a variety of responses. We are currently studying this process with attention to both advantages (e.g., oral vaccination) and disadvantages (e.g., food allergies).

References

1. Hashizume F. et al. (2008) Development and evaluation of transgenic rice seeds accumulating a type II-collagen tolerogenic peptide. Transgenic Res., 17:1117-1129.
2. Okumura H. et al. (2007) Association of chicken zona pellucida glycoprotein (ZP) B1 with ZPC induces formation of ZPB1-ZPC fibrous aggregates containing disulfide-bridged ZPB1 dimer. Biochim. Biophys. Res. Commun., 364: 682-688.
3. Aoki N. et al. (2007) Identification and characterization of microvesicles secreted by 3T3-L1 adipocytes: redox- and hormone-dependent induction of milk fat globule-epidermal growth factor 8-associated microvesicles. Endocrinology, 148: 3850-3862.
4. Okumura H. et al. (2007) Heterocomplex formation and cell-surface accumulation of hen's serum zona pellucida B1 (ZPB1) with ZPC expressed by a mammalian cell line (COS-7): a possible initiating step of egg-envelope matrix construction. Biol. Reprod., 76: 9-18.
5. Nakatani H. et al. (2006) Weaning-induced expression of a milk-fat globule protein, MFG-E8, in mouse mammary glands, as demonstrated by the analyses of its mRNA, protein and phosphatidylserine-binding activity. Biochem. J., 395: 21-30.
6. Okumura H. et al. (2004) A newly identified ZP glycoprotein, ZPD, and dimeric ZP1 of chicken egg-envelope are involved in sperm activation on sperm-egg interaction. Biochem. J., 384: 191-199.
7. Aoki, N. & Matsuda, T. (2002) A nuclear protein tyrosine phosphatase TC-PTP is a potential negative regulator of the PRL-mediated signaling pathway: dephosphorylation and deactivation of Signal Transducer and Activator of Transcription 5a and 5b by TC-PTP in nucleus. Mol. Endocrinol., 16: 58-69.
8. Usui, Y., et al. (2001) A 33 kDa allergen from rice (Oryza sativa L. Japonica): cDNA cloning, expression and identification as a novel glyoxalase I. J. Biol. Chem., 276: 11376-11381.
9. Takeuchi, Y. et al. (2001) Morphological and biochemical changes of isolated chicken egg-envelope during sperm penetration: Degradation of the 97kDa glycoprotein is involved in sperm-driven hole formation on the egg-envelope. Biol. Reporod., 64: 822-830.
10. Aoki, N. & Matsuda, T. (2000) A cytosolic protein tyrosine phosphoatase PTP1B specifically dephosphorylates and deactivates prolactin-activated STAT5a and STAT5b. J. Biol. Chem., 275: 39718-39726.

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