Laboratories

Laboratory of functional Biomolecules Engineering(National Institute of Advanced Industrial Science and Technology; AIST) Recruiting students for the academic year 2018

Molecular and Cellular Breeding Research Group

Professor Shinya HONDA
National Institute of Advanced Industrial Science and Technology; AIST
+81-29-862-6737
E-mail: s.honda{at}aist.go.jp
Lab HP

Introduction

【Key Words】protein engineering, evolutional molecular engineering, synthetic biology, biologics, therapeutic proteins

 The excess of imports over exports of pharmaceutical products exceeds 2 trillion yen in Japan. Thus, most of national medical expenses finally flow abroad. This unfavorable balance of trade in medical economy must be solved so that such an expenditure leads, for example, new capital spending and creates the healthy employment. Therefore, the achievement of the armaceutical products with “Japanese flag”through the domestic innovation in drug development and manufacture,especially for biologics, is demanded among other things. Hence we aim at the construction of fundamental technologies to contribute to innovative development and manufacture for biologics, and push forward a research of protein engineering and synthetic biology with the both theoretical and experimental approaches.
 As concrete subjects, we are conducting the following theme:analysis of the molecular evolution of proteins using a cross profiling method that is the computational technique developed by us, development of designing software for an artificial protein based on the energy landscape sampling, synthesis of artificial proteins with novel structure and high function by evolutional molecular engineering method,engineering yeast cells having a synthetic genetic circuit for drug development screening,analysis of the tolerance acquisition mechanism of drug-resistantgenes,development of the pharmacokinetics improvement technology of biologics, stabilization of pharmaceutical protein using post-translation modification mechanism, construction of the library for screening drug-like molecules having a non-immunoglobulin scaffold,and advancement of the quality control technology for biologics using the artificial affinity protein. Through these, we aim at the holistic understanding of biological system in association with evolution and the offer of valuable industrial applied seeds of engineering. We welcome every person who wants to spend his or her student life in the atmosphere of National Institute which is different from that of universities. Please refer to a homepage for the details.


Bio Production Research Institute, Synthetic Bioengineering Research Group

Professor Kentaro MIYAZAKI
+81-29-861-6033
E-mail: miyazaki-kentaro{at}aist.go.jp
Lab HP

Introduction

【Key Words】evolutional molecular engineering, metagenomics, ribosome engineering, synthetic biology, white biotechnologyn

 Research in my group focuses on (i) functional metagenomic, (ii) evolutionary engineering of enzymes and (iii)ribosome engineering. These technologies are integrated to develop microorganisms (mostly Escherichia coli) to diversify or improve microbial functions

Funktional metagenomics.

 It is known that more than 99% of microorganisms are thought to be unculturable or difficult to culture in a laboratory using standard cultivation methods. We apply functional metagenomics approach to screen for industrially relevant enzyme-coding genes that are otherwise difficult to be discovered.
Refs) Curr Opin Biotechnol 20:616-22(2009);ISME J 3:1335 -48 (2009);Environ Microbiol 9:2289-97 (2007)

Evolutionary engineering of enzymes.

Enzymes are environmentally friendly biocatalysts that are widely used in modern life. One roadblock to more widespread use of enzymes in industry is their lack of stability under nonnative conditions, e.g., extremes of pH, temperature, and ionic strength that are common to industrial bioprocesses. This problem can be partly solved by genetically modifying the protein via rational design or directed evolution. Such protein engineering may also improve other enzymatic properties (e.g., enhanced substrate specificity, expression level, and reduced product inhibition,etc.)that are crucial to industrial bioprocesses. We develop various genetic engineering techniques that are valuable for directed evolution and apply them for improving enzyme’s functions.
Ref) J Biol Chem 281:10236-42(2006);Trends Biochem Sci26:100-6(2001);J Mol Biol 297:1015-26(2000)

Ribosome engineering.

 The ribosome is an extremely complex molecule in its structure and function. Because of this complexity,it was considered that the molecule is difficult to engineer. Recently, we have shown that ribosome can be modified for its function by replacing one of the central components 16S rRNA. We apply this technique to address to the question on the robustness of life (or ribosome)and to use thus engineered organisms for industrial applications.
Ref) Nat Commun 2:549 (2011);PNAS 109:19220-5(2012)


Biological Clock Research Group

Professor Katsutaka OISHI
+81-29-861-6053
E-mail: k-ooishi{at}aist.go.jp
Lab HP

Introduction

【Key Words】Chronobiology, Biological clock, Circadian rhythm, Chrono-nutrition, Sleep

 Endogenous oscillators control the variety of physiological and behavioral circadian rhythms of almost all life forms from bacteria to humans. The suprachiasmatic nucleus (SCN)is the master circadian pacemaker that controls most physical circadian rhythms such as sleep/wake cycles,body temperature, blood pressure, heart rate, hormonal secretion and metabolism, as well as behavior in mammals. Numerous studies at the molecular level have suggested that the circadian oscillator in the SCN is driven by negative feedback loops consisting of the periodic expression of clock genes. Studies of clock genes in mammals have implied that oscillatory mechanisms function in various peripheral tissues such as the heart,lung,liver,kidney,and circulating blood cells, and that they are entrained to the SCN. Although the peripheral oscillators seem to play an important role in regulating various physiological functions, the circadian oscillatory mechanism in peripheral tissues remains vague. We are trying to understand the circadian regulation system in the organism at the molecular levels.
 Recent studies on the clock genes reveal the relationships between the circadian clock and the appearance or symptom of various diseases. Moreover, increases in the sleep disorders, depression, and the neurosis etc. are also thought to be associated with the circadian clock disturb in the 24 hours society. Development of a novel treatment method through a circadian clock regulation seems to become possible, because strong connections exist between the circadian clock disruption and the metabolic disorders under various diseases. We are aiming to pay attention to not only the contribution to the time-dependent medical treatment and the chronopharmacology fields but also the relationships between the lifestyle (especially, feeding habit and mental stress) and circadian clocks at a molecular level, and to contribute from a preventive viewpoint to the public health medical treatment.
 1)Molecular mechanisms of the circadian rhythm generation by the biological clock in culture cells to animals
 2)Search for functional molecules that potentially regulate the circadian clock.
 3)Relationships between the circadian clock and various diseases such as metabolic diseases (diabetes, obesity, and thrombosis), cancer, sleep disorders, depression, and other mental stress.


Bioanalytical Research Group

Associate Professor Naohiro NODA
+81-29-861-6039
E-mail: noda-naohiro{at}aist.go.jp
Lab HP

Introduction

 We develop novel bioanalytical technologies for the characterization of nucleic acids and proteins. Further,we are working with biomolecule standard materials and contributing to biotechnology standardization. We aim toward the industrial application of the developed technologies in collaboration with private companies. Our laboratory is an environment where you can experience research work and obtain knowledge regarding industrial applications and standardization techniques.

Development and standarization of bioanalytical methods.

We develop standard materials for the validation and evaluation of bioanalytical methods. These standard materials are used in medical engineering and genetic testing fields. In these fields,non-SI-traceable methods are used to determine the amount of nucleic acids and proteins. In order to overcome such situations,our laboratory is trying to use digital PCR and fluorescence correlation spectroscopy, which can directly quantify the number of biomolecules such as nucleic acids and proteins, to establish SI-traceable methods. Moreover, the development and evaluation of nucleic acid reference material are conducted in our laboratories and we are standardizing bioanalytical methods to facilitate the global use of biotechnology in many fields. To facilitate the standardization of biotechnology, we have constructed a framework for cooperation with domestic industrial bodies and foreign governmental/research institutes.

Development of drug-screening techniques targeting nucleic-acid related enzymes.

Nucleic-acid-related enzymes such as helicase, nuclease, polymerase, and ligase are indispensable for all organisms. These enzymes play vital roles in the cell life cycle of all organisms and it is important to elucidate the mechanisms underlying their effects. We focus on the toxin-antitoxin (TA) systems, a nucleic-acid-related enzyme that is widely conserved among microorganisms. It is known that toxin molecules can cause growth arrest and death of microorganisms under stress conditions. Thus, the TA system is considered to be a potential drug target. We are conducting 1) expression and purification of toxin/antitoxin proteins and 2) development of screening methods for functional molecules that potentially regulate TA systems.

We welcome students who are interested in the development of bioanalytical technology,international standards for biotechnology, and the unique TA systems in microorganisms. We promise that you will have an excellent experience with us.

Laboratories

The University of Tokyo
Graduate School of Frontier Sciences, The University of Tokyo

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