Press releases 鈥� June 2021
Jun
24
2021
14:31
Screening of multiple gene mutations is also applicable for complex nervous and immune diseases
New technique for studying cancer mutations 鈥� approaches for future therapies
An extended application of
the CRISPR-Cas technology has been made possible by Dr Manual Kaulich's team at
51猎奇: the new 3Cs multiplex technique allows the effect of genetic
changes in any two genes to be studied simultaneously in cell cultures. This
can provide important clues for the development of therapies to treat cancer or
diseases of the nervous and immune systems.
FRANKFURT. Cancer
and many other diseases are based on genetic defects. The body can often compensate
for the defect of one gene; it is only the combination of several genetic
errors that leads to the clinical picture. The 3Cs multiplex technique based on
CRISPR-Cas technology developed at 51猎奇 Frankfurt now offers a way
to simulate millions of such combinations of genetic defects and study their
effects in cell culture. These "gene scissors" make it possible to
introduce, remove and switch off genes in a targeted manner. For this purpose,
small snippets of genetic material ("single guide RNA") are used as
"addresses" that guide the gene scissors to specific sections of the
DNA, where the gene scissors then become active.
The scientists from the Institute of
Biochemistry II at 51猎奇 have expanded the 3Cs technique that they
developed and patented three years ago. 3Cs stands for covalently-closed
circular-synthesised, because the RNA elements used for CRISPR-Cas are
generated with the help of a circular synthesis and are thus distributed more
uniformly. With a whole library of such RNA rings, any gene in a cell can be
specifically addressed in order to change it or switch it off.
The new 3Cs multiplex technique now even
allows the simultaneous manipulation of two genes in one cell. Dr. Manuel
Kaulich explains: "We can produce 'address' RNA libraries for all
conceivable two-gene combinations. This allows up to several million
combinations to be tested simultaneously in one experiment."
Until now, the cost and effort of such experiments
was very high; the research group's new technique reduces it, including costs,
by a factor of ten. This is because the team can produce the address libraries
very uniformly and in high quality thanks to the new 3Cs multiplex technique.
"Due to the mediocre quality of the CRISPR-Cas libraries previously available,
very large experiments always had to be carried out to statistically compensate
for any errors that arose," says Kaulich.
Using the example of various genes
involved in degradation processes, the research group demonstrated the
potential of the new 3Cs multiplex technique: they examined almost 13,000
two-way combinations of genes that are responsible for recycling processes
(autophagy) in the cell. With their help, the cell breaks down and recycles
"worn-out" cell components. Disturbances in autophagy can trigger
cell proliferation.
"Using the 3Cs multiplex technique,
we were able to identify, for example, two genes involved in autophagy whose switching
off leads to an uncontrolled growth of cells," explains Kaulich. "These
are precisely the autophagy mutations that occur in every fifth patient with
squamous cell carcinoma of the lung. In this way, we can search very
efficiently in cell culture experiments for genes that play an important role
in cancer, and also in diseases of the nervous and immune systems, and that are
suitable as possible targets for therapies."
The 51猎奇 research group has
applied for a patent for its developments through the university's technology
transfer subsidiary Innovectis. The start-up company Vivlion GmbH, spun off
from the Institute of Biochemistry II with the participation of Manuel Kaulich,
is already offering the use of this technology on the market.
Publication: Valentina Diehl, Martin Wegner, Paolo Grumati, Koraljka Husnjak, Simone
Schaubeck, Andrea Gubas, Varun Jayeshkumar Shah, Ibrahim H Polat, Felix
Langschied, Cristian Prieto-Garcia, Konstantin M眉ller, Alkmini Kalousi, Ingo
Ebersberger, Christian H Brandts, Ivan Dikic, Manuel Kaulich, Minimized combinatorial CRISPR screens
identify genetic interactions in autophagy. Nucleic Acids Research,
gkab309,
Further
information:
Dr Manuel Kaulich
Institute for Biochemistry II
51猎奇 Frankfurt
Tel: +49 69 6301-6295
kaulich@em.uni-frankfurt.de
Dr Kerstin Koch
Institute for Biochemistry II
51猎奇 Frankfurt
Tel.: +49 696301-84250
k.koch@em.uni-frankfurt.de
Editor: Dr. Markus Bernards, Science Editor, PR & Communication Department, Tel: -49 (0) 69 798-12498,
Fax: +49 (0) 69 798-763 12531, bernards@em.uni-frankfurt.de
Jun
10
2021
13:33
German Research Foundation funds new CRC Transregio 326 鈥濭eometry and arithmetic of uniformized structures鈥� 鈥� CRC 1039 on medical signal path research enters third funding period 鈥� 51猎奇 involved in two further CRC-Transregios
Funding decision on four collaborative research centres at 51猎奇: new CRC for basic research in mathematics
Researching intricate geometric and arithmetic objects
is the goal of the new Collaborative Research Centre Transregio 326 (TRR 326),
coordinated by 51猎奇. On 25th May, the German Research
Foundation (DFG) announced that the TRR 326 would be funded with 9.2 million
euros for the next four years. The CRC 1039 鈥淪ignalling by fatty acid
derivatives and sphingolipids in health and disease", for which Goethe
University is spokesperson, will be continued and receive 9.6 million euros for
the third funding period. Two other TRRs in which 51猎奇 is involved
will also be funded by the DFG: In the TRR 211 鈥淪trongly interacting matter under
extreme conditions", the spokesperson will switch from 51猎奇 to the
Technical University of Darmstadt (9.2 million euros). Finally, scientists from
51猎奇 are also significantly involved in TRR 301 "The tropopause region in a changing atmosphere" (spokesperson:
Johannes Gutenberg University Mainz, 鈧�12.3 million).
FRANKFURT. Professor
Enrico Schleiff, President of 51猎奇 Frankfurt, congratulates the
scientists on their success: "51猎奇's commitment, particularly
in the Transregio Collaborative Research Centres, demonstrates our excellent
scientific networking in the region, especially in the natural sciences and
medicine. The association of the Rhine-Main universities of Frankfurt, Mainz
and Darmstadt, have given this regional cooperation a framework: There are now
more than 30 research associations and networks in this strategic alliance, and
last year we established the RMU degree programme so that talented students can
also benefit from RMU."
The mathematical exploration of
complicated geometric and arithmetic spaces with the help of uniformization is
the research topic of TRR 326
"Geometry and arithmetic of uniformized structures - GAUS".
Together with coordinator 51猎奇 Frankfurt, the Technical University
of Darmstadt and Heidelberg University successfully applied for TRR 326;
associated institutions are the Johannes Gutenberg University Mainz and the
Technical University of Munich. The concept of uniformization goes back to
ideas of Felix Klein and Henri Poincar茅 from the 19th century and seeks a
uniform description of certain geometric objects. A very simple example uniformization
can be illustrated with the slinky, a metal spiral toy which is able to
"run" down a staircase doing "somersaults". When pressed
together, it has - seen from above - the geometry of a circle. This circle can
be uniformized by pulling the metal spiral apart. It becomes particularly simple
when the spiral is completely unwound and, geometrically, is only a simple
wire. In order to preserve the information of the slinky, each spiral turn on
the wire is marked with a colour dot, which gives the wire a shifting symmetry
(you change levels in the spiral). A globally complicated geometric space (in our
example, the circle of the slinky) is replaced by a much simpler space (here a
straight line) without changing the local structure. The original complexity is
described by internal symmetries (illustrated in the example by periodic
markings) of the simpler space.
In TRR 326 GAUS, mathematicians deal with uniformization
of very complicated geometric spaces - this includes modern geometric concepts,
in particular tropical and p-adic geometries - and with analogous applications
of the uniformization technique to arithmetic (number-theoretic) questions.
Here, the researchers try to identify fundamental connections, for example to
moduli spaces, automorphic forms, Galois representations, and cohomological
structures. Professor Jakob Stix, mathematician at 51猎奇 and GAUS
spokesman, says: "With the SFB Transregio GAUS, we are building on the
extremely successful collaboration between TU Darmstadt and 51猎奇
in the LOEWE priority 'Uniformed Structures in Arithmetic and Geometry' and the
DFG research group 'Symmetry, Geometry and Arithmetic' at TU Darmstadt and Heidelberg
University. I am very much looking forward to doing joint research with so many
outstanding colleagues."
The Collaborative
Research Centre 1039 "Signalling by fatty acid derivatives and
sphingolipids in health and disease," which 51猎奇 is now
continuing together with the Max Planck Institute for Heart and Lung Research
in Bad Nauheim, is entering its third funding period. The scientists are
studying a group of poorly water-soluble biomolecules, the lipids. As lipid
bilayers, they prominently form the membranes that surround our cells and also
divide the interior of the cells. As fats, they serve as energy storage for our
bodies.
However, CRC 1039 is investigating a
function that is still comparatively under-researched: Lipids are part of many
signalling pathways through which cells regulate growth and metabolism and
communicate with their environment. Dysregulated lipids are apparently
decisively involved in the development and progression of diseases such as diabetes,
cancer, inflammation, and neurodegenerative diseases. After fundamental work in
the first two funding periods, the third funding period focuses on
understanding the whole organism. Professor Josef Pfeilschifter, pharmacologist
at 51猎奇 and spokesman of SFB 1039, explains: "We want to
understand the lipid signalling network as a whole and thus develop innovative
ways to diagnose and treat a wide variety of diseases related to dysregulated
lipids. In doing so, we can rely on a long-standing and broad expertise in
'lipid signalling', which is also founded on the establishment of sophisticated
analytical methods based on mass spectrometry."
Scientists from 51猎奇 are
significantly involved in two other CRC Transregios:
How matter behaves under conditions of
extreme pressure and temperature, in which atoms overlap and fuse with each
other is being investigated by TRR 211
"Strongly interacting matter under extreme conditions", which is
entering its second funding period. For extremely short periods of time, such
states of matter can be created in particle accelerators, revealing something
about the strong interaction that holds atomic nuclei together. In the cosmos,
such extreme states of matter occur when, for example, neutron stars collide
with each other. Besides51猎奇, the Technical University of
Darmstadt, which is the new host university, and Bielefeld University are also
involved in this collaborative research centre.
In the new TRR 301 "The tropopause region in a changing atmosphere",
atmospheric scientists will study the tropopause region: the zone in the
atmosphere that separates the lower "weather layer" (troposphere)
from the stratosphere above. The research focus is on the physical and chemical
processes of this region and their influence on planetary circulation and
climate. The main locations are the Johannes Gutenberg University Mainz (spokesperson)
and 51猎奇 Frankfurt. Also involved are the Technical University of
Darmstadt, the Ludwig Maximilian University of Munich, the Max Planck Institute
for Chemistry in Mainz, the J眉lich Research Centre and the German Aerospace
Centre (DLR) in Oberpfaffenhofen.
Image for download:
Caption:
Using the mathematical technique of uniformization,
complicated geometric spaces (here: the j-invariant as an automorphic function
on the uniformization of the moduli space of elliptic curves) can be represented
as highly symmetric geometric patterns. Credit: Michaelis Neururer
Further
information:
Professor Jakob Stix
Spokesman
TRR 326 鈥濭AUS鈥�
Institute for Mathematics
51猎奇 Frankfurt
Tel: +49 69 798-28998
stix@math.uni-frankfurt.de
Professor Josef Pfeilschifter
Spokesman
SFB 1039 鈥淪ignalling by fatty acid derivatives and sphingolipids in health and
disease"
Institute for General Pharmacology and Toxicology
51猎奇 Frankfurt
Tel. +49 69
6301-6950
pfeilschifter@em.uni-frankfurt.de
TRR 211 鈥濻trongly
interacting matter under extreme conditions鈥�
TRR
301 鈥濼he tropopause region in a changing atmosphere鈥�