SPOTLIGHT 3469
Development 139, 3469-3470 (2012) doi:10.1242/dev.087700
© 2012. Published by The Company of Biologists Ltd
An interview with Haruhiko Koseki
Haruhiko Koseki is Director of the Developmental Genetics Research Group at the RIKEN Research Center for Allergy and
Immunology in Yokohama, where he studies the epigenetic regulation of Polycomb group genes in development. He recently
joined Development as an Editor, and agreed to be interviewed about his research and about science in Japan.
When did you first become interested
in developmental biology?
I started university in the school of
medicine, and became fascinated with
comparative anatomy and embryology. In
medical school in Japan, the first 4 years
consist of basic classes, and the last 2 years
are clinical training. I didn’t enjoy clinical
training very much, and decided to move to
immunology research instead of becoming
a clinician. At that time, the field of
immunology was exploding, and the
discovery of the rearrangement of
immunoglobin genes led to the study of cell
differentiation in that field. My PhD
research was in immunogenetics, but I
discovered that immunology is not really the
field to be in to study differentiation or
patterning. Because of that, I made the
decision to move to developmental biology.
I did my postdoc with Rudi Balling in
Freiburg (Germany), working on
development based on mouse genetics. I
really enjoyed life in Freiburg, and during
my time there I published my first paper in
Development.
Interview by Eva Amsen*
Online Editor, Development
*Author for correspondence
([email protected])
When I was in Germany, I learned that, in
Japan, science is not fundamental science,
but it’s science aimed at technology. We’re
always asked about the social benefit of our
discoveries. That is a natural question to ask,
but I think, in Europe, people just appreciate
science for the discovery.
Another difference used to be the budget
invested into science. Until recently, it was
much smaller in Japan compared with
Europe or the USA, but in the last few
decades this has changed, and at the
moment it’s not very different from Europe.
But I’m not sure our productivity is at the
same level as that of European scientists. I
think we’re not very good at sharing
resources, infrastructure or ideas. It also
seems that Japanese postdocs and students
are not interacting much with each other.
They’re relatively quiet and shy compared
with European students. Traditionally, we’re
educated to behave as modestly and quietly
as possible. But now we have many foreign
students and postdocs, and I think many
students are starting to notice that this shy
attitude is not ideal to get ahead in science.
What are you currently working on?
I’m mostly studying the epigenetic
regulation underlying the maintenance of
certain cell types and differentiation. When
I did my postdoc in Freiburg, I was
investigating how the notochord regulates
somite differentiation, but when I got back
to Japan in 1994, I realized that field is so
competitive. I didn’t want to do similar
things to what everyone else was already
doing. At that time, my main interest was
axial skeletal patterning. In the early 1990s,
many people working on mammalian axial
patterning were looking at Hox and
signalling cascades. In Drosophila,
Polycomb was already known to be a very
important regulator for anterior/posterior
specification, so I decided to work on
Polycomb in the mouse. I used the system
developed by Andras Nagy in Toronto
(Canada) to generate many knockouts for
components
of
mouse
Polycomb
complexes. Knockouts enabled us to see
whether the mammalian Polycomb proteins
are doing something important during
development, but it’s difficult to address the
underlying mechanisms by using
developing embryos because of their
cellular heterogeneity. To bypass this issue,
we’re now focusing on ES cells as a model
to study Polycomb function, to find out how
various Polycomb complexes cooperate to
maintain certain cell types and how their
functions are modified when cells
differentiate into different states. Now the
critical issue is learning how catalytic
activities and chromatin binding of
Polycomb complexes are regulated during
cell cycle progression. Ideally I’d want to
get back to real embryos, but for that we
need more technical breakthroughs – maybe
a new device to image the chromatin status
of certain loci in the living embryo, or
something like that.
What are some other projects that
your research group is working on?
Most of us are working on various aspects
of Polycomb function. Polycomb proteins
form at least a few multimeric protein
complexes, but each component also
interacts with many other modules, outside
of
Polycomb
complexes,
during
differentiation or cell cycle progression, and
approximately half of my research group is
studying these interactions. For example,
work with knockout mice shows that the
axial skeleton phenotype of the DNA
methyltransferase mutant is very similar to
that of the Polycomb knockout. That
suggests that there could be a functional and
profound interaction between Polycomb
and DNA methylation mechanisms, and
that’s one of the things we’re investigating.
This is a big challenge for us because of its
extensive complexity and redundancy.
You also administer the mouse facility
at your institute. Who uses this
facility?
The mouse facility is shared by the five
different institutes that make up the
Yokohama RIKEN site. The animal facility
DEVELOPMENT
How does research in Japan compare
with research in Europe?
3470 SPOTLIGHT
How have you experienced your first
few months as a Development
Editor?
It’s a great pleasure, but I’m still getting
accustomed to the job, so it’s still taking up
a lot of time. This is my first experience as
an academic editor, and I learned a lot in the
last few months, particularly from
reviewers’ comments. Geographically,
we’re very isolated in Japan, and not
readily exposed to the way science is
discussed and evaluated in the USA or
Europe. Now, through reviewer comments,
I get a look into how people are thinking
about papers and how they express their
views.
Are there any particular papers that
you would really like to see people
submit to Development?
Developmental biology is linked to several
other fields. For example, imaging is
becoming
very
quantitative
and
mathematical modelling is now used to
describe
developmental
processes.
Unfortunately, genomics is still a bit far
from developmental biology, because of the
heterogeneity of cells and quantitative
limitations of samples. With technical
breakthroughs such as chromatin
immunoprecipitation, the field of genomics
is moving closer to developmental biology,
but many genomics researchers don’t
consider their work in that context. There
might eventually be a lot of genomics
studies that are very interesting in terms of
developmental biology, but genomics
researchers might not think of submitting
them to Development. The same is true, for
example,
for
transcriptome
and
metabolome studies.
What would people be surprised to
find out about you?
I have played volleyball since I was a high
school student. I didn’t have a lot of
opportunity to play when I was in
Germany, unfortunately, but except for
these 3 years in Freiburg, I have kept
playing. I’m now 50, and that’s old in terms
of playing volleyball. Ten years ago, I had
a fracture on my right ankle and it took
almost half a year to recover. Recently, I’m
a bit cautious of getting injured. But I still
join in competitive games and sometimes
go to the other side of Japan for
competitions.
DEVELOPMENT
is mainly used by the immunologists, but is
increasingly also occupied by people from
the institutes for human genetics, ‘omics’
sciences and plant sciences. This suggests
that mouse genetics is becoming a more
general tool to address a wide spectrum of
biological and medical questions. Mouse
genetics has developed in parallel with
immunology, developmental biology and
neurosciences, and will be further advanced
by collaborating with many other fields of
biomedical sciences, as well as other
disciplines. It is really exciting to see with
my own eyes how things are developing in
this field. I am particularly interested to see
the upcoming contribution of mouse
genetics to the understanding of pathogenic
mechanisms underlying various human
diseases.
Development 139 (19)