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

4 PORTRAIT
The Helmholtz Centre for Infection Research
Our name reflects the scientific programme: At the
Helmholtz Centre for Infection Research in Braunschweig
approximately 350 scientists and 350 employees from
technology and administration lay the foundations for new
prevention methods, diagnostic procedures, medicines and
active agents with which infectious diseases can be better
treated or more effectively prevented. The paths that lead to
this goal are as varied as the paths by which the pathogens
enter our bodies. Microbiologists investigate how bacteria
and viruses manage to enter our bodies, how bacteria
communicate with one another and how exactly they make
us ill. Geneticists investigate our genetic make-up in search
of reasons why one person falls ill with flu, for example,
whilst his neighbour does not. Immunologists investigate
how organisms react to an intruder and resist it. Structural
biologists research the molecular structures of key molecules
with all of their interactions. Chemists use this
knowledge to investigate and develop new agents that can
in turn be employed to combat pathogens. Vaccine researchers
have their sights set on the best way to combat germs:
they aim to prevent these from making us ill at all.
New diagnostic approaches, vaccines or medicine can only
be successfully developed when the mechanisms of
infectious diseases have been properly understood. A
starting point from which researchers at the Helmholtz
Centre for Infection Research approach the complex
network of “infection” is the cell - both that of the host and
that of the bacteria. One example: opportunistic infections.
These are a problem in hospitals. In a place where patients
with weakened immune systems are treated, bacteria
transform themselves from unobtrusive companions to
dangerous aggressors. In extreme cases they ensconce
themselves permanently in our bodies by forming a
so-called biofilm, causing chronic illness under certain
circumstances. In biofilms the bacteria are surrounded by a
protective sheath that protects them very effectively against
attacks from the immune system or antibiotics. But what
has to occur in order for a seemingly harmless germ to
become an aggressor? How do bacteria communicate with
one another and the host? Only when scientists have
understood how the pathogens and their host cells interact
and which are the mechanisms behind these interactions
they can disrupt the communication between bacteria in a
targeted manner.
Infections are always caused by molecular interactions
between humans and pathogens and between the pathogens
themselves. Central element of this interplay are the
proteins involved in infections. These consequently play a
key role in the comprehension of infectious diseases. The
microorganisms organise and catalyse their life with
thousands of proteins. The goal of infection researchers is
not only to describe these proteins but also to understand
their functions. The proteins on the cell surface, in particular,
are responsible for the contact with the host – and the
question hanging over the research remains: how do bacteria
manage to infect us? The arsenal of these different pathogenity
factors, with which bacteria, viruses and other microbial
pathogens interfere with the process of human cells is a
modest one – however, knowing where these are located and
being able to name these factors does not yet mean that they
are understood. Proteins are very large molecules with
complex structures and it is precisely in these structures that
the secret of their success lies. The scientists at the HZI take
a close look at their structure - atom for atom. They look for
niches and hooks with which they brush alongside one
another, cling to and release one another.
Once the structural biologists have familiarised themselves
with these decisive parts of the molecular structure the
chemists can begin to put this knowledge to further use.
Their goal is to develop tailored molecules that fit this
structure exactly - and subsequently have the opportunity
to interrupt an infection. To this end chemists look for
natural inhibitors or create new synthetic ones, using these
to block the functions of the pathogen proteins in a targeted
approach.
The basis for new active agents, which can then attack the
weak points of the bacterial proteins, are often natural
agents. These originate in traditional, recently rediscovered
healing plants, from fungi or bacteria. A special role in the
HZI research is played by the myxobacteria. These live in
the soil and defend themselves against bacterial com petitors
with a range of chemical substances - substances that are
highly effective when precisely analysed by infection
researchers and then developed into medicines. Microbial
active agent principles for combating infectious diseases
are therefore seen as the optimal initial substances for
developing new therapies against bacteria for use in
hospitals.