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A Rapid and Efficient Cell Sorting Method Allows New Insights into Early Animal Embryogenesis - Close Collaboration between Max Delbrück Center and New York University

Caenorhabditis elegans (C. elegans) is one of the most important model systems in biology. A technique to collect large numbers of embryos of the animals, all precisely the same age, has been developed in a collaborative effort by researchers from the Max Delbrück Center (MDC) in Berlin, Germany and New York University (NYU), USA. This new technique (termed eFACS) and subsequent molecular analysis of small RNAs are reported online this week in Nature Methods (DOI 10.1038/nmeth.1370). eFACS opens the door for detailed and quantitative high-throughput studies of early events during embryogenesis of C. elegans, a prerequisite for Systems Biology approaches. Using eFACS, the researchers were already able to reveal that small RNA expression during early embryogenesis is a highly orchestrated and complex process.  

C. elegans is an important animal model
for biologists and many genes essential for the early events in mammalian
embryo development have been identified in the worm.

Yet, to
date, it has not been possible to collect large numbers of embryos at the same
developmental stage, a prerequisite to studying gene expression and protein
interactions on a genome-wide scale with novel high-throughput genomics or
biochemistry assays, which in term are necessary for Systems Biology
approaches.

“The current
method of choice is collecting embryos by hand”, Marlon Stoeckius, one of the
two lead authors from the MDC-research group of Nikolaus Rajewsky explains.
“This is very time consuming and does not yield adequate sample size for
large-scale studies.”

Nikolaus
Rajewsky and colleagues together with Fabio Piano at New YorkUniversity
established a method (termed eFACS), using fluorescence-activated cell sorting
(FACS), to efficiently and rapidly collect tens of thousands of embryos at the
same stage within a few hours. They use embryos that express a stage-specific
protein fused to a fluorescent marker; when the embryo reaches the particular
stage, it fluoresces.

Making use
of eFACS, the scientists carried out high-throughput sequencing to profile
small RNA populations in various embryonic stages, and gained insight into how
gene expression changes during the first cell cycles in a worm embryo.

They
discovered complex and orchestrated changes in the expression between and
within almost all classes of small RNAs, including microRNAs, during
embryogenesis. Small RNA molecules play an important role in the regulation of
genes.

The
researchers are convinced that eFACS will make a contribution towards a more
complete understanding of gene regulatory networks during early animal
development.

PhD Exchange Program between MDC and NYU

Marlon
Stoeckius is the first PhD-student in the new program the MDC and NYU have set
up to train PhD-students. Nikolaus Rajewsky was a Professor at NYU before he
joined the MDC.

This
program is a collaboration between the new Berlin
Institute for Medical Systems Biology (BIMSB), headed by Nikolaus Rajewsky at
the MDC and the new Center for Genomics and Systems Biology at New YorkUniversity, headed by Fabio Piano. It
will support scientific exchange between the two complementary institutions on
either side of the Atlantic Ocean.

The basic
concept of this new program is that collaborative PhD projects are performed in
Berlin and New York and that each graduate student is
jointly supervised by a Principal Investigator from each of the two research
institutions. PhD students have the opportunity to divide their time between Berlin and New
York, as Marlon Stoeckius has done for his research
on C. elegans.

The BIMSB
is funded within the program “Advanced Research and Innovation in the New
States” by Germany’s
Federal Research Ministry (BMBF). In 2008, the BIMSB received a kick-off
funding of 7.5 Million euros by the BMBF and 4.4 million euros by the Senate of
Berlin.

*Large scale sorting of C. elegans embryos reveals the dynamics of small RNA expression.

Marlon Stoeckius1,4, Jonas Maaskola1,4, Teresa Colombo1,3, Hans-Peter Rahn1, Marc R. Friedländer1, Na Li1, Wei Chen1, Fabio Piano2,* & Nikolaus Rajewsky1,*

1 Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Str. 10, 13125 Berlin, Germany

2 New York University, Department of Biology and Center for Comparative Functional Genomics, 100 Washington Square East, New York, NY 10003, USA.

3 present address: Dipartimento di Biotecnologie Cellulari ed Ematologia, Sezione di Genetica Molecolare, Università La Sapienza, Rome, Italy

4 equal contributions

*corresponding authors: fp1@nyu.edu and rajewsky@mdc-berlin.de

Barbara Bachtler
Press and Public Affairs
Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch
Robert-Rössle-Straße 10; 13125 Berlin; Germany
Phone: +49 (0) 30 94 06 - 38 96
Fax:  +49 (0) 30 94 06 - 38 33
e-mail: presse@mdc-berlin.de
http://www.mdc-berlin.de/
 

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