research

The cellular processes involved in the maintenance of cellular activity, including, cell movement, growth and replication, responses and adaptation to the environment, energy metabolism and biosynthesis rely on an extremely complex network of interacting biomolecules from which emerge the basic properties of life. The thorough understanding of such processes is an immense challenge even for some of the most basic living organisms such as the bacterium E. coli, a common human digestive tract inhabitant. However, we believe this simpler model organism is a logical starting point to begin such an ambitious project. Moreover, there are good reasons to believe that this simpler life form will also reveal mechanisms that will be broadly applicable to more complex eukaryotic and multicellular organisms. While the metabolic pathways and biology of E. coli are among the best characterized, numerous uncharacterized components and activities remain to be discovered. In addition, E. coli is also starting to reveal that it may be a unicellular organism but it also has a complex social life.

Biofilms: development and functional differentiation

Biofilms are large collectives of microbial cells embedded in an extracellular matrix composed of proteins and polysaccharides. Biofilms have unique properties that are thought to protect the cells from various environmental challenges.

There is also accumulating evidence the cells within biofilms differentiate into metabolically distinct populations. As P.W. Anderson (1972) said, more is different!

We are exploring this process from different biochemical and imaging perspectives using E. coli. It displays a more sophisticated social life than we originally suspected and we are trying to explore this aspect of socio-microbiology.

biofilm_video.mov

Time-lapse video recording of the development of an E. coli biofilm growing on agar

Video: Hidden secrets of bacteria revealed through systems biology

A presentation for the TEDxTohokuUniversity 2020 conference about the Hidden Life of bacteria.

Provides an overview of some of our research findings and interests in bacterial systems biology.

From the caption: "... bacterial cells are also part of a micro-economic system where growth, cellular activity and interactions between cells produce complex dynamical structures and phenomena that are not unlike those in our own societies."

Omics analysis of E. coli cellular phenotype

Large scale omics analysis of RNA, proteins and metabolites in E. coli can reveal mechanisms of adaptation to grow under different environmental conditions or following the gene deletion of metabolic enzymes.

The first large-scale integrated omics analysis of E. coli

In this groundbreaking study we characterized molecular changes in E.coli following both environmental (growth rate) changes and single gene deletions of most of the central carbon metabolism enzymes.

Ishii et al. 2007

Perspective in Science

Science STKE (EDITORS' CHOICE)

Multi-omics analysis of E. coli following adaptive evolution on glycerol

Here, we clarified some of the metabolic changes and mechanisms that allow E. coli to grow nearly as fast on glycerol (a poorer carbon source) than on glucose following adaptive evolution.

Cheng et. al. 2014

Enzyme discovery

MERMAID method

We developed novel methods based on untargeted metabolome analysis, to reveal unknown enzymatic activities. In our MERMAID method, isolated proteins are incubated with mixtures of metabolites, incubated and then analyzed for identifying changes in metabolites triggered by the protein. From this we can infer the reaction, provide a specific function to a proteins and with some extra work reveal its physiological functions.

The E. coli Yhhy protein

Using a simpler, more focussed, approach we could assign an amino acid acetylase activity to the previously uncharacterized protein YhhY. The results show that acetylation occurs on histidine, methionine and phenylalanine both in vitro and in vivo in E. coli cells. The exact physiological function of YhhY still remains to be elucidated.

see: Iuchi et al, 2015 (PDF)

Data analysis and bioinformatics

Software solutions, such as MathDAMP and JDAMP were developed, in collaboration with colleagues, to facilitate the analysis of complex metabolome profiles. These tools can highlight specific and statistically significant differences in profiles, a task that is otherwise very tedious and time-consuming.

MathDAMP

MathDAMP facilitates the visualization of differences between metabolite profiles acquired by hyphenated mass spectrometry techniques. Differences are highlighted by applying arithmetic operations to all corresponding signal intensities from whole raw (automatically preprocessed and normalized) datasets on a datapoint-by-datapoint basis. The results are visualized using density plots.

Baran et al. 2006

TriDAMP extension

JDAMP

JDAMP (Java application for Differential Analysis of Metabolite Profiles) is a collection of easy-to-use tools for analyzing capillary electrophoresis-mass spectrometry (CE-MS) data.

This software based on the MathDAMP algorithm, subtracts background drifts, removes noise, aligns datasets, and helps to quickly visualize significant differences among multiple samples.

Sugimoto et al. 2010

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