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Development of a novel method for producing biopharmaceutical

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HOHSAKA Lab.
Senior Lecturer:WATANABE Takayoshi

E-mail:
[Research areas]Chemical Biology, Biotechnology, Bioorganic Chemistry
[Keywords]Artificial Protein, Biopharmaceutical, Antibody, Non-natural Amino Acid, Caged Compound, Nucleic Acid, Biomolecule

Skills and background we are looking for in prospective students

It is desirable to be interested in chemistry and biology. A wide range of knowledge and skills such as genetic engineering, protein science, and organic chemistry is required for advancing research. These can be acquired while the research process.

What you can expect to learn in this laboratory

Our research is based on a broad range of knowledge and skills such as genetic engineering, protein science, organic chemistry, and cell culture, so that you are able to acquire these specialized knowledge and skills. Furthermore, you can learn the ability to tackle things from various perspectives. In addition, logical research promotion ability and problem-solving skills can be acquired through research activities.

【Job category of graduates】
Companies related to chemistry and biology

Research outline

Modification of functional molecules such as fluorescent groups and photo-responsive molecules to proteins makes it possible to impart artificial functions to proteins. As a technology for artificial functionalization of proteins, we have developed a method for site-specific incorporation of non-natural amino acids into proteins and a technology for position-specific modification of functional molecules to proteins. Currently, we are engaged in research for development of novel methods that enable the creation of biopharmaceuticals by leveraging our previous research results and findings. Our research themes include the following:

1. Development of antibody-drug conjugate with site-specific drug modification

“Antibody-drug conjugate” in which an agent such as an anticancer drug is bound to an antibody has been made possible to efficiently deliver a drug to a target cell by using high antigen specificity of the antibody. However, in the conventional method for synthesizing antibody-drug conjugate by randomly modifying the drug against the lysine and cysteine residues in the antibody, there was concern that the activity of the antibody would be reduced. Therefore, we address to apply the site-specific chemical modification method of the proteins which we have developed to the synthesis of antibody-drug conjugate (Figure 1).
Furthermore, we also develop antibody-drug conjugate capable of releasing drugs to target cell by light irradiation by giving photo-responsive function to the drug using organic synthesis method. And we are engaged in the research aiming at putting these methods into practical use as the creation technology of the antibody-drug conjugate.


Figure 1. Scheme for synthesis of antibody-drug conjugate

2. Development of new technology to promote protein expression

Biopharmaceuticals such as insulin as a drug for diabetes and interferon as a drug for hepatitis are generally synthesized in microorganisms or cultured cell by using genetic engineering methods. However, depending on the type of protein, the expression efficiency of protein in living cells is low. Therefore, general and widely applicable methods for enhancing expression efficiency of protein are required. By focusing on the fact that the mRNA secondary structure influences the protein expression, we are currently engaged in development of a new method for improving the expression efficiency of protein by controlling the mRNA secondary structure.

3. Development of biopharmaceuticals containing non-natural amino acids by molecular evolution

We have developed a method that enables molecular evolution of aminoacyl-tRNA synthetase mutants by using liposome which encapsulated cell-free translation system. By using this method, we are currently engaged in the research aiming to develop novel biopharmaceuticals containing non-natural amino acid with enhanced activity by molecular evolution within liposome.

Key publications

  1. K.P. Huynh Nhat, T. Watanabe, et al., Antibody-based fluorescent and fluorescent ratiometric indicator for detection of phosphotyrosine. J. Biosci. Bioeng., 122, 146-154 (2016).
  2. A. Uyeda, T. Watanabe, et al., Liposome-based in vitro evolution of aminoacyl-tRNA synthetase for enhanced pyrrolysine derivative incorporation, ChemBioChem 16, 1797-1802 (2015).
  3. T. Watanabe, et al., Synthesis of nucleobase-caged peptide nucleic acids having improved photochemical properties, Org. Biomol. Chem. 12, 5089-5093 (2014).

Equipment

High Performance Liquid Chromatography (HPLC), Mass Spectrometry (MALDI-TOF MS), Fluorescent Scanner, Cell Culture System

Teaching policy

In our laboratory, the development of novel method for producing biopharmaceutical by combining the knowledge and skills of chemistry and biology is proceeded. After laboratory assignment, we instruct a broad range of knowledge and experimental skills necessary for performing your research. Through these processes, we teach you to understand the significance of promoting research by combining various research fields. And, by reducing instructions from us gradually, we teach you to acquire the ability to tackle research independently through trial and error. Furthermore, by providing opportunities not only for discussion in the laboratory but also for presentation at the research conference, we aim to nurture students who have mastered communication skills that can be used in society.

[Website] URL:http://www.jaist.ac.jp/ms/labs/hohsaka/

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