current projects

Ecological Systems Biology – Self-Organization and Function of Microbial Ecosystems


Looking at the nature that surrounds us, we find an enormous diversity and complexity. The underlying mechanisms are often poorly understood, mostly because natural ecosystems are hard to access experimentally. In my current research I am looking for these underlying principles by using microbial ecosystems in the lab that are easy to access, control and manipulate. I am especially interested in how ecosystems organize themselves by species interactions. I try to find biophysical explanations of how microbial interactions work and shape microbial communities in composition and spatial organization.



 

microbes community interactions Picture: Wikimedia

microbial interactions

Microbes usually exist in communities consisting of myriad different but interacting species. These interactions are typically mediated through environmental modifications; microbes change the environment by taking up resources and excreting metabolites, which affects the growth of both themselves and also other microbes. A very common environmental modification is a change of the environmental pH. Here we show that changing and reacting to the pH leads to a feedback loop that can determine the fate of bacterial populations and the interactions between different species.Thus understanding how single species change the pH and react to it allowed us to estimate their pairwise interaction outcomes.

[PLOS Biology, 2018]


ecological suicide in microbes

Organisms can display negative interactions by changing the environment in ways that are detrimental for them, for example by resource depletion or the production of toxic byproducts. We found an extreme type of negative interactions, in which bacteria modify the environmental pH to such a degree that it leads to a rapid extinction of the whole population, a phenomenon that we call ecological suicide. We found ecological suicide in a wide variety of microbes, suggesting that it could have an important role in microbial ecology and evolution.

[Nature Ecology and Evolution, 2018]

highlighted in Nature, Süddeutsche Zeitung and New York Times


bacteria ecocide


criticality biodiversity collapsePicture from New York Times

anthropogenic loss of biodiversity

In nature an enormous amount of organisms coexists. However in many cases a sudden loss of this biodiversity can be observed: single species take over and dominate the ecosystems, which causes massive damage to ecosystems and extinction of many species. Often this happens in combination with human influence like over-fertilization or overexploitation of natural resources. I want to explore why this sudden breakdown of coexistence happens and how we can counteract it to protect natural biodiversity.


Self-organized patchiness

Ecosystems are highly structured. Organisms are not randomly distributed but can be found in spatial aggregates at many scales leading to heterogeneity up to regular patterns. On the one hand abiotic factors are causing those patches but also intrinsic factors - like the interaction between the organisms - seem to play a major role. Beside the emergence of those heterogeneities even more their function remains unclear. I am using a microbial system to explore how patchiness can arise by intrinsic factors and what the ecological meaning of the emerging heterogeneities might be.

[Nature Microbiology, 2016]


bacterial self organized patches



Fish swarm aggregation allee effect Picture: Wikimedia

Collective movement

Many organisms actively form aggregates. Just think of bird or fish swarms, insect colonies or flocks of mammals. To do so those organisms have to synchronize the movement. Movement and decisions have to become collective instead of individual. I am investigating how the transition from equally distributed organisms to aggregates takes place, what the driving forces and what the potential benefits of active group formation are.

biological invasion

The increasing transport of goods and people around the globe also leads to unwanted transfer of organisms between largely separated areas. Sometimes they are able to settle and thrive in the new environment, leading to drastic changes in ecosystems. This may lead to massive damage and large efforts have been made to contain such invasions. I want to investigate how invasions can be early detected, their harmfulness estimated and counteractions taken.


invasion network global transport Global airline routes. Picture: Wikimedia
 


Past projects:

Heat shock protein 90

and its investigation by single molecule FRET



Hsp90 crystal structure X ray When cells are exposed to elevated temperatures, cytosolic proteins start to unfold, misfold and aggregate. To keep the cell alive under those conditions so called heat shock proteins are expressed. Most of them are Chaperones, proteins that are able to bind unfolded and misfolded proteins, stop aggregation and support their refolding. Heat shock protein 90 (Hsp90) is one of those chaperones playing an essential role also in the unstressed cell. Hsp90 is a dimer consisting of two elongated chains lying in parallel to each other. It can turn over ATP and undergoes large conformational changes. Moreover its function of modified by small proteins - so called Cochaperones.  I investigate the dynamics of Hsp90 by means of single molecule multicolor FRET. During my work I could resolve the conformational cycle of yeast and bacterial Hsp90 showing large differences between both systems. Whereas bacterial Hsp90 is strictly nucleotide controlled, yHsp90 is mainly thermally driven.  Anyway this little dependence of yHsp90 on ATP turnover allows a much richer controlling by Cochaperones. For more detailed information look at the specific projects and corresponding publications.

--> Animation of the principle of single molecule FRET


Hsp90 cochaperone interaction observed by four color FRET

yeast Hsp90 - contrary to bacterial Hsp90 - does not work on its own in the cell but is modified in its function by small proteins - so called Cochaperones. To learn more about the function of those cochaperones I investigated the interaction of Hsp90 with the Cochaperone Sba1 and nucleotides. Four color FRET allowed the simultaneous observation of Hsp90 dynamics in interplay with Sba1 and nucleotide binding.

Nat.Comm., 2014, highlighted in Nature Methods
Hsp90 P23 interaction investigated by four color FRET
evolution of Hsp90 mechanism

Evolution of the Hsp90 mechanistics

yeast Hsp90 shows a mechano-chemical cycle which does not consist of a successive order of processes but is strongly dominated by thermal fluctuations (see below). To learn more about evolution of this uncommon protein mechanism the bacterial Hsp90 was investigated with single molecule two and three color FRET. In contrast to the situation in yeast bacterial HtpG is massively controlled by nucleotides and shows a successive ATPase cycle following a mechanical ratchet mechanism. Thus Hsp90 evolved from a strongly nucleotide controlled system to a very stochastic mechanism.

--> Animation of the conformational cycle of HtpG

JMB, 2012




mechano-chemical cycle of Hsp90 observed by three color FRET

Rich dynamics at both the N- and C-terminal end of yeast Hsp90 could be found (see below). Anyway its correlation with ATP turnover remained enigmatic. To directly observe the interaction between ATP turnover and conformational dynamics I constructed a three color single molecule FRET setup. It turned out that Hsp90 can bind ATP both in the N-terminally open and closed state whereas ATP does not force Hsp90 into a specific conformational state. Both conformational changes as well as nucleotide binding are strongly stochastic events. Thus Hsp90s mechano-chemical cycle is dominated by thermal fluctuations.
 
PNAS, 2012




Hsp90 ATP binding investigated with three color FRET
C-terminal dynamics of Hsp90 obsered with single molecule FRET

C-terminal dynamics of Hsp90

Beside a N-terminal dimerization site yeast Hsp90 also has a C-terminal dimerization site which was up to this project regarded as permanently closed, because of the overall large stability of the Hsp90 dimer. Anyway with a two color single molecule FRET measurement rich dynamics also at the C-terminal part of Hsp90 could be found. Moreover this C-terminal dynamics are influenced by binding of nucleotides to the opposite N-terminal part of Hsp90. Thus a long distance communication pathway exists throughout the whole Hsp90 protein. This long distance communication moreover allows an anti-correlation between the N- and C-terminal dynamics.

PNAS, 2010




N-terminal dynamics of Hsp90

Hsp90 is an ATPase which undergoes large conformational changes. Mainly moving from a V-like open structure to a pretty compact closed structure. Anyway up to this work it was believed that the turnover of ATP drives these conformational transitions. With a single molecule FRET assay it could be shown that those open-closed transitions also take place in the absence of ATP and are only slightly modified by the presence of ATP. Thus the large conformational changes of yeast Hsp90 are only weakly coupled to ATP turnover.

Nat.Struct.Mol.Biol., 2009
Obervation of Hsp90s N-terminal dynamics with single molecule FRET

              








































































































four color  FRET Setup