Molecular and Cellular Biology

From small RNAs to megadalton sized protein complexes, the sophisticated functions of living cells are carried out by thousands of different molecules. They generate energy, transmit signals, move components, and coordinate cellular events in space and time. How do these molecules work – individually and as part of larger ensembles - to control the cell’s activity? At the IMP, the groups in Molecular and Cellular Biology use synergistic approaches to tackle these questions.  Strong scientific support and technology developments in protein chemistry, bio-optics, electron microscopy, and genomics provide an experimental foundation to functionally dissect the molecular mechanisms of the cell.  Atomic structure determination, single molecule biochemistry and system-wide cellular analyses address function at multiple scales, providing a comprehensive view of how molecular mechanics control cellular biology.

Clausen Group

The misfolding and aggregation of protein molecules is a major threat to all living organisms. For example, aggregated proteins accumulate in several neurodegenerative diseases like the Alzheimer's, Parkinson and Huntington's disease. Cells have therefore evolved a sophisticated network of molecular chaperones and proteases to prevent protein aggregation. The Clausen group studies the structural, biochemical and functional basis of prokaryotic and eukaryotic factors that combat folding stress and, in parallel, ensure controlled digestion of specific target proteins.

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Cochella Group

Small non-coding RNAs are emerging as versatile regulators of gene expression in all kingdoms of life. In particular, microRNAs have been shown to play important roles in diverse cellular functions, in processes ranging from cell-type differentiation during development to controlling local translation at the synaptic terminals of an active neuron. Our lab focuses on how miRNAs themselves are generated in a cell-type and stage-specific manner and how they integrate with the rest of the cellular genetic networks in order to fulfill their specific functions. To address these questions we use a variety of molecular biology and genetics tools available for the nematode C. elegans.

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Marlovits Group

Membrane associated processes are a fundamental property of all living cells.  They guarantee that cells can effectively communicate with and consequently adapt to their environment.  They do this by either physically translocating molecules to the opposite site of a membrane or by receiving, transmitting and amplifying incoming signals.  The Marlovits laboratory is studying the molecular mechanism of such processes by using structural, biochemical and genetic approaches. In particular, the laboratory is focusing on machineries, which are critical to the biology of many animal and plant pathogens and addresses how bacterial toxins are translocated into eukaryotic cells.

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Obenauf Group

Metastasis is the colonization of distant organs by circulating tumor cells. It represents the final stage of cancer progression, and causes 90% of cancer related deaths. Current treatment regimen frequently fail to provide durable clinical responses, because cancer cells re-wire various tightly regulated cellular processes that make them extremely efficient in utilizing survival signals, evading immune-mediated killing, and adapting to new environments. The Obenauf group dissects these metastasis-related cellular programs in cell culture systems and mouse models, and integrates the obtained results with clinical data. The goal is to understand the mechanistic determinants of tumor formation, metastatic colonization, and drug resistance to identify new cancer cell vulnerabilities and drug targets.

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Pauli Group

Embryogenesis – the development of a single cell into a fully patterned organism - is one of the most fundamental yet complex biological processes. While most of the signaling pathways and genes that are essential for embryonic development had generally been assumed to be known, recent studies discovered that many regions outside of the annotated protein-coding open reading frames (ORFs) are translated, raising the intriguing possibility that new embryonic regulators remain to be identified. While some of these translated regions are predicted to encode short proteins/peptides whose conservation often suggests functional importance, others lack signatures of protein conservation and might have regulatory roles. The Pauli lab investigates the functions of these newly discovered translated regions in the context of embryonic development, using zebrafish as a model organism.  

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Pavri Group

Antibodies form the basis of all long term serum immunity against pathogens and thus lie at the very core of a healthy immune response. The process by which the immune system generates the vast repertoire of pathogen-specific antibodies from a limited set of genes is called antibody gene diversification. This diversity occurs in the germline of the antibody-encoding Immunoglobulin (Ig) locus of B lymphocytes via a complex interplay of transcriptionally-coupled focused mutagenesis, non-homologous recombination and DNA repair. The Pavri group investigates the molecular mechanisms regulating this phenomenon by utilizing a broad combinatorial approach involving mouse genetics, molecular immunology, RNAi-based screening, cellular imaging and genomics.

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Peters Group

To pass the genome from one generation to the next, human cells first generate two copies of each of their 46 chromosomes. These copies, called sister chromatids, remain connected until they are separated from each other during mitosis, so that two genetically identical daughter cells can be formed. The Peters Group studies how sister chromatids become connected by a protein complex called cohesin, and how the removal of cohesin from chromosomes in mitosis initiates the separation of sister chromatids. The lab is also addressing how cohesin affects the structure and function of the genome when it is packaged in chromatin.

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Westermann Group

Cells have evolved complex and extremely precise chromosome segregation mechanisms, which ensure that genetic information is passed correctly from one generation to the next.  In order to understand how the cell moves chromosomes during mitosis, the Westermann Group is studying the structure, function and regulation of the kinetochore, a complex multi-protein assembly that connects chromosomes to dynamic microtubules. In a reductional biochemical approach they aim to study and assemble functional kinetochores from their constituent parts in vitro. In addition, the lab uses yeast genetics to manipulate and engineer simple chromosome segregation systems in vivo.

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Mass Spectrometry & Protein Chemistry

Mass spectrometry (MS) has emerged as a core analytical technique in protein chemistry. Driven by the rapid development of instrumentation, analysis methods and computing tools, MS based proteomics is at the forefront of techniques in modern life sciene research.
In the Mechtler lab, we are interested in developing new methods to increase the sensitivity, accuracy and precision of protein identification/quantification and the detection of post translational modifications. Our aim is to use these optimized methods to answer fundamental biological questions.

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