Martin Hällberg

Microbial single and multi-species communities are ancient survival modes of organisms. If present at inappropriate locations, those matrix-embedded multicellular life forms, commonly called biofilms, are detrimental in clinical, industrial and agricultural settings. Although biofilm formation of organisms has been extensively studied on the molecular and single cell level, the nano-scale interaction of extracellular matrix components within biofilms and with surfaces has much less been explored. Using innovative photon, electron and neutron based technologies predominantly available at synchrotron sources in combination with microbiological, genetical and biochemical approaches this project will tackle nano-scale interactions between the components of the extracellular matrix with the aim to further develop rationalized interference strategies. Thereby, analysis of biofilms of organisms such as Pseudomonas aeruginosa with biofilm formation a major virulence factor in chronic infections

model organisms such as Salmonella typhimurium and Escherichia coli which form biofilms using ubiquitous ancient matrix components and multispecies biofilms which are known to significantly alter the biofilm physiology will be conducted. The spectrum of to be investigated biofilms ensures a broad coverage of biologically relevant interactions, the identification of common principles and optimal differential development of innovative sensitive methodologies at synchrotron sources.

Mitochondria are the power plants of the eukaryotic cell and disturbed mitochondrial function causes a wide range of genetic diseases. Although gene expression from mitochondrial DNA is of key importance for maintaining mitochondrial function, the molecular basis of mitochondrial gene expression is largely unexplored. Transcription from mitochondrial DNA results in long polycistronic transcripts that need extensive processing and maturation to obtain the functional RNA units that are necessary for mitochondrial translation. Here, we propose to determine the molecular basis of key steps in the mitochondrial gene expression machinery: DNA replication, initial RNA processing and mRNA maturation/stabilization. To this end, we will use a unique combination of biochemistry, biophysics and structural biology techniques. Understanding these processes on the molecular level is critical for our understanding of fundamental aspects of mitochondrial gene expression and will, in the long term, enable new treatments for important mitochondrial diseases.

The central dogma in molecular biology means that the genetic information is transferred from DNA via RNA to protein. In this process, transcription factors are needed for a gene (DNA) to start copying to RNA, that is, for the transcription to start. There are generic and regulatory transcription factors. The regulatory transcription factors are controlled by a variety of signals inside and outside the cell. In cancer cells, this signaling is often incorrect and incorrect transcription factors are activated and activated all the time. The transcription factors act in the cell nucleus but are produced out in the cytoplasm and therefore need to be transported into the cell nucleus in order to function. The proposed research is to understand how certain cancer-critical transcription factors are recognized at a molecular level when they are transported into the nucleus and perform their work. The technique we use is called protein x-ray crystallography, a method by which one can determine exactly how a protein, or in this case a protein complex, looks in three dimensions. By understanding how specific cancer-relevant transcription factors are recognized by the cell transport machinery at a molecular level, we allow the extension that we with drugs can inhibit their transport into the cell nucleus and thereby prevent further cancer growth. The drugs that can thus be tailored to certain cancer-critical complexes of proteins have high specificity and thereby have side effects. Furthermore, these drugs work differently from traditional cancer drugs, which opens the way to successful combination therapies.