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Mechanism and Biology of RNA Silencing

The Ameres lab studies fundamental biological mechanisms of post-transcriptional gene regulation through pathways with enormous biological, biomedical, and technological impact.

Keywords: Post-transcriptional gene regulation, RNA biochemistry, RNP enzymology, RNA modifications, small non-coding RNAs

Mechanisms of Epigenetic Memory

Animals and plants develop from a single fertilised germ cell into thousands of specialised cell types within the adult. Cell identities are specified by differential gene expression programs from the single genetic blueprint. Epigenetic memory helps to maintain these distinct programs. Our group investigates the mechanisms that govern epigenetic memory in vertebrates. We use synthetic biology approaches in mouse stem cells to “reprogram” epigenetic chromatin modifications and study their dynamics and mode of inheritance. Our goal is to identify the regulatory mechanisms that help to maintain gene expression states through the massive chromatin reorganisation that occurs during genome replication and cell division.    

Keywords: epigenetics, chromatin, development, polycomb, histone modifications

Transposon silencing  & heterochromatin formation by small RNAs

There is an ongoing arms race between eukaryotic genomes and transposable elements. The Brennecke lab studies the biology and mechanism of an RNA interference system that silences transposons in animal gonads—the piRNA pathway. piRNA-mediated repression of transposons is crucial for fertility and thus species survival. Research into this genome surveillance pathway has produced remarkable discoveries in various fields – such as small RNA biology, gene silencing, heterochromatin formation, epigenetics, and gametogenesis. We combine genetics, genomics, and biochemical approaches to uncover the molecular principles that underlie key features of the piRNA pathway: its enormous potency and specificity in silencing, and its ability to constantly adapt to challenges posed by new and evolving transposons.

Keywords: transposons, piRNAs, heterochromatin, epigenetics, small RNAs

Functional Genomics in Embryonic Stem Cells   

Embryonic stem cells represent the immortal in vitro capture of a very early stage of mammalian development. They maintain the potential to give rise to all cell types of the body and therefore carry the promise to transform our understanding of development and treatment of disease. The Elling lab studies embryonic stem cell biology using forward genetic screens by employing and optimizing state-of-the-art screening technologies such as haploid genetics and CRISPR/Cas9. We probe stem cell biology and ask questions about lineage maintenance, lineage transition, and the underlying epigenetic programs.     

Keywords: haploid, screen, CRISPR/Cas, embryonic stem cell, cell fate

Assembly and function of the cell division machinery

Proliferating cells undergo dramatic reorganization during mitosis to properly partition their organelles to daughter cells. Upon mitotic entry, interphase organelles transiently acquire a form that can be mechanically segregated to the two nascent daughter cells. For instance, mitotic chromosomes form non-membrane-bounded bodies, separated from the cytoplasm by regulated surface properties. These organelles subsequently restore their interphase morphologies during mitotic exit. Our group investigates how human cells reorganize internal components during the cell cycle to ensure their precise distribution. We use multi-disciplinary approaches, including cell biology, biophysics, biochemistry, and computational biology. Our goal is to understand how molecular components reshape macroscopic cell structures through self-organization.

Keywords: mitosis, chromosomes, cell organelles, high-content screening, computer vision, biophysics

Linear Ubiquitination in inflammation, cell death and autophagy    

We are interested in ubiquitin - a dynamic modification that diversifies protein function by altering any of a number of features, including structure, stability and interacting partners. Given its broad range of effects and substrates, protein ubiquitination regulates and coordinates many biological processes at the molecular, cellular and organismal levels. Our group studies how ubiquitin networks control inflammation, cell death and autophagy. We use multiple approaches to tackle this question, from biochemistry techniques to genetically modified animal models. Ubiquitin molecules link together to form chains with different topologies on their target proteins, depending on which enzymes link them together. These different topologies recruit distinct complexes and effectors that specifically regulate various aspects of physiology. We are particularly interested in understanding the mechanisms and biology of a non-classical topology: linear ubiquitination. 

Keywords: Ubiquitin signal, E3 ligase, immune responses, cell death, autophagy

Brain development and disease

The human brain is the most complex of all organs. In the Knoblich lab, scientists are fascinated by the mechanisms that lead to the assembly of this fascinating biological structure. For this, we use a unique combination of model organisms ranging from insects to humans. To understand, how neural stem cells form the right neurons at the right time and how tumors form when this process goes wrong, we analyze the simple nervous system of the fruit fly Drosophila. To analyze those processes in humans, we grow human fetal brain tissue in vitro starting from pluripotent stem cells that we obtain from patients. By working with clinical research groups, we can derive 3D culture models for neuro-psychiatric disorders and analyze their developmental origin. Our unique combination of model organisms allows us to analyze human disease in a deeply mechanistic manner. Our analysis of brain development will illuminate the etiology and potential therapies for cancer, neurodegeneration, and other neurological disorders.

Keywords: stem cell, brain, organoids, cancer

Homeostatic regulation of adult stem cells

Homeostatic turnover in adult tissues is thought to be the outcome of an orchestration of signalling pathways governing differentiation and proliferation. Upon tissue damage, adult stem cells rapidly proliferate to restore lost cells and reinstate homeostasis. This response is triggered by local damage-induced signals that promote proliferation and differentiation of adult stem cells. De-regulation of these processes can result in either hyperplasia or in a depletion of tissue and adult stem cells. The signals regulating homeostatic turnover and injury response are largely unknown. The Koo lab aims to understand the cellular and molecular mechanisms that govern the biological processes of homeostatic turnover, tissue injury-repair and pre-neoplastic transformation.

Keywords: adult stem cells, organoids, genetics, E3 ubiquitin ligases, cancer


Thomas Marlovits*

Design and function of molecular machines

What keeps cells and organisms alive are specific functions performed by highly organized macromolecular assemblies. Thomas Marlovits' research group wants to understand the architectural design of these ‘biological nanomachines’. The team explores such structures under normal and disease-related conditions. In order to elucidate the molecular mechanisms, the research group uses high-resolution three-dimensional electron microscopy to directly visualize molecular machines in action.

*Thomas Marlovits is a joint IMP-IMBA group leader and about to leave to the CSSB - Centre for Structural Systems Biology, Hamburg in autumn 2017.

-> Marlovits-Lab-Homepage

Molecular control of human organogenesis

Organs consist of multiple tissues that develop from embryonic precursors by patterning, self-organisation and maturation. The fascinating journey from patterned tissue progenitors to functional organs is not understood, especially not for human development and disease. Based on developmental insights, the objective of the Mendjan lab is to pattern lineage precursors in vitro, and discover the mechanisms that drive self-organisation and maturation of tissues into mesodermal organ-like structures. Our approach is to use human pluripotent stem cell (hPSC) differentiation into cardiac and adipose tissues to decipher the molecular control of organogenesis, and of associated disorders. 

Keywords: Organogenesis, human pluripotent stem cells, mesoderm, cardiac, adipose, patterning

Modeling Human Disease

The Penninger lab aims to uncover the roles of specific genes in development and in the etiology of disease. We have established novel approaches to manipulate gene function and to model different diseases in vitro and in vivo. Our goal is to establish basic principles of physiology and basic mechanisms of disease pathogenesis, with an emphasis on heart and lung diseases, cancer, as well as neurological and bone disorders. Armed with this knowledge, we can develop novel therapies and treatment strategies.

Keywords: embryonic stem cells, organoids, development, cancer, disease, mouse models

CHROMATIN REPROGRAMMING IN TOTIPOTENT STEM CELLS

Within a matter of hours, fertilization transforms highly differentiated cells - gametes -  into a single totipotent cell with the potential to give rise to a complete organism. Gametes like egg and sperm are generated by meiosis. Meiotic chromosome segregation in eggs becomes more error-prone in females as they age, leading to trisomic pregnancies and aberrant embryonic development. The Tachibana-Konwalski lab studies both the causes of age-related chromosome missegregation in eggs and the natural reprogramming that occurs after fertilization to produce a totipotent embryo. How chromatin loses the epigenetic memory of a differentiated gamete state and is reprogrammed to a state of totipotency remains poorly understood. We use mechanistic cell biology, 3D spatial chromatin organization, 4D live-cell imaging and mouse molecular genetics to investigate how chromatin is reprogrammed in totipotent embryos. Our goals are to uncover the mechanisms that underlie the oocyte maternal-age-effect and zygotic reprogramming, which could illuminate new therapeutic strategies for reproductive and regenerative medicine.   

Keywords: totipotency, stem cells, chromatin organization, epigenetic reprogramming, zygotes, oocytes

Systemic Regulation of Adult Neurogenesis

Neural stem cells in the hippocampus generate new neurons throughout life. These neurons play crucial roles in learning, memory and mood. Our lifestyle, including exercise, diet and stress, influences adult neurogenesis. Depression and impaired memory are associated with declines in adult neurogenesis. Our group investigates how systemic metabolism regulates the activity of adult hippocampal stem cells. We use transgenic approaches to label adult neural stem cells and track their responses to genetic or dietary changes.  We are also using patient-derived cell lines to study how human neural stem cell behaviors are modulated by genetic changes and drug treatment. Our goals are to uncover mechanisms that regulate adult neural stem cells and potential strategies to treat disorders associated with aberrant adult neurogenesis. 

Keywords: brain, stem cells, niche, metabolism, memory, emotions

FORMER IMBA RESEARCH GROUPS
Barry DicksonInformation processing in defined neural circuits and complex behavior in DrosophilaJanelia Research Campus
Thomas MarlovitsDesign and function of molecular machinesCSSB Centre for Structural Systems Biology
Javier MartinezRNA metabolism in mammalian cellsMFPL Max F. Perutz Laboratories
Kazufumi MochizukiSmall RNA-directed DNA elimination in TetrahymenaInstitute of Human Genetics, Montpellier, France
Leonie RingroseQuantitative EpigeneticsIRI Life Sciences, Humboldt University, Berlin, Germany
Vic Small (Emeritus Group)Cell MotilityThe Cytoskeletion and Cell Migration