Cell News 2/2016
12
Binder Innovation Prize:
Melina Schuh
Summary
We aim to understand meiosis in mammalian oocytes, the proge-
nitor cells of eggs. This topic is of great interest for fundamental
research because meiosis is still only poorly understood, especially
in mammals. It is also of direct medical relevance because defects
in eggs are the leading cause of pregnancy loss and several con-
genital diseases such as Down’s syndrome. Our main aim is to un-
derstand how defects at the interface between chromosomes and
cytoskeletal structures lead to aneuploid eggs and pregnancy loss
in mammals. To this end, we study how the meiotic spindle is or-
ganized, how it segregates the chromosomes and how the spindle
interacts with actin to drive the meiotic divisions. To have a solid
foundation for future research, we are developing new tools to
study meiosis in mammalian oocytes. For instance, we have been
able to carry out the first high content screen for meiotic genes
in mammals. We have also been able to establish methods that
now allow us for the first time to study the causes of chromosome
segregation errors directly in live human oocytes. This has opened
an exciting new area of research in our laboratory that we plan to
expand significantly in the future.
Introduction
Human life starts with the fusion of an egg and a sperm. Egg and
sperm develop in a process called meiosis. But despite its impor-
tance, meiosis is still much more poorly understood than mitosis,
especially in mammals. Many fundamental questions that have
been studied extensively in mitotic cells, such as how chromoso-
mes are segregated, how the spindle assembles, and how cells are
organized internally have hardly been addressed in mammalian
eggs. Thus, studying meiosis in mammalian oocytes is of great inte-
rest from a basic research point of view. In addition, it is of medical
relevance: depending on the age of the woman, around 10-50%
of human eggs are chromosomally abnormal (Kuliev et al., 2005;
Kuliev et al., 2011; Rosenbusch and Schneider, 2006). This makes
aneuploidy in eggs the most common cause of pregnancy losses
and human aneuploidy such as Down’s syndrome (Brar and Amon,
2008; Nagaoka et al., 2012).
Most abnormalities in eggs result from errors during the meiotic
divisions (Fig. 1) (Clift and Schuh, 2013). An egg develops out of
a progenitor cell called an oocyte. Oocytes are stored in the ovary
Figure 1: Meiosis and
fertilization in mam-
malian oocytes.
In the
upper row, the different
stages of meiosis in
mammalian oocytes
and the corresponding
large scale chromoso-
me (red) and microtu-
bule (green) organiza-
tion are shown. In the
lower row, the detailed
configuration of a pair
of homologous meta-
centric chromosomes is
shown. © Melina Schuh
Marian Schott (Sales Representative Bavaria & Austria, BINDER GmbH),
Ralph Gräf, Melina Schuh
DGZ AWARD WINNERS 2016
