Research Report 2010 2011 - Helmholtz-Zentrum für ...

SCIENTIFIC REPORTS | TWINCORE, Centre for Experimental and Clinical Infection Research GmbH
143
well-characterized homoserine lactone signal molecules P.
aeruginosa produces a third interbacterial signal molecule,
the Pseudomonas quinolone signal (PQS). PQS is involved
in cell density dependent virulence factor regulation – as
well as the homoserine lactone – and is essentially involved
in the establishment of P. aeruginosa biofilms. However, the
molecular mechanism of the implementation of the PQS signal
in a bacterial behaviour at the signal cell level is largely
unknown. Here, a pqsE encoded enzyme, the last gene in
the PQS biosynthetic operon, seems to play a central role.
The elucidation of the function of PqsE is a key research
focus of our group.
The workgroup of Prof. Dr. Ott: (from left to right) Johan Waern,
Michael Rothe, Martin Pacher, Michael Ott, Urda Rüdrich,
Gesa Riedel, Quinggong Yuan, Ina Rittelmeyer (missing:
Michael Bock). Photo: Twincore/HZI
Prof. Häußler and her team: (from left to right) Vera Nöding,
Kathi Klimmek, Susanne Häußler, Mathias Müsken, Andrea
Blanka Photo: Twincore/HZI
Research group Prof. Dr. Michael Ott |
ott.michael@mh-hannover.de We develop cell and gene
therapy procedures for the treatment of hereditary liver
disease. Another focus lies on the development of mouse
models with chimeric human/murine liver tissue and human
immune system for researching vaccination strategies
against HIV and HCV. The repopulation of the liver with
human liver cells and the transplantation of human blood
stem cells into immune deficient mice continue to represent
a major scientific challenge. In order to investigate vaccination
strategies in the alb-uPA transgene immune deficient
(RAGyc) mouse it is necessary that human cells of a donor
are utilised in the repopulation of the mice. Where primary
tissue is used as starting material the isolation of both cell
populations using foetal liver tissue exclusively is possible.
In our transplantation experiments it emerged that the transplantation
of foetal hepatoblasts is significantly less efficient
than that of adult primary hepatocytes. Alternatively, the
research group enabled the transplantation of foetal human
liver tissue beneath the capsule of the recipient liver to be
tested for the first time. The first combined transplantations
of human blood stem cells and foetal liver tissue to a newlydeveloped
mouse strain are set to be performed shortly. Due
to the lack of availability of primary human cell material for
the “humanisation” of mice, as well as for cellular therapies
in humans, the research group is conducting intensive research
into alternative cell sources. In association with MHH
groups and international partners, research is underway into
hepatic differentiation protocols for embryonic stem cells
and iPS cells. In another project the risk of insertional mutagenesis
in lentiviral gene transfer is being analysed. Serial
transplantation of ex vivo genetically transduced hepatocytes
enables the incidence of liver tumours in dependence on the
number of lentiviral insertions to be investigated. Furthermore,
the research group is supervising a clinical study on
cell transplantation in patients with urea cycle disorder.
This project marks the world’s first controlled study on cell
therapy of hereditary metabolic diseases of the liver.
TWINCORE key publications In 2010 employees working at
TWINCORE published a total of 54 articles. In 2011 already
24 articles have either been published or are “in press” (see
“Complete list of articles published in 2010 as well as articles
published an “in press” in 2011 by employees working
at TWINCORE”). Particularly important research results
have been compiled in the following areas:
1. Regulatory T cells in the immune modulation therapy
So far, proven therapeutic vaccination against tumours
have shown only minimal or no success. Now we have succeeded
in improving the therapeutic vaccination success
in the treatment of malignant melanoma in a mouse model
by selective depletion of regulatory T cells (Klages et al.,
2010). Another project made an important contribution to a
better understanding of the regulatory mechanisms of the
immune system in the intestine (Sawa et al., 2011).