Research Groups

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 cells, cell fate

THEORETICAL MODELS OF CHROMOSOME STRUCTURE

Each human cell contains a staggering amount of DNA – billions of molecular basepairs that would stretch up to 6 meters in length if placed end-to-end! Imagine a cell magnified 100,000 times – it would have a nucleus one meter in diameter containing genomic DNA in 300 spools of thin fishing line – 3000km long and 0.2 mm in diameter. Not only do cells have to access the tightly packed DNA for transcription to RNA, genomes must be accurately duplicated, disentangled and passed along to daughter cells, all while maintaining them intact. To perform these basic functions reliably in a variety of organisms and conditions, evolution has come up with complex machinery and creative mechanisms, some of which we study in our lab using computational – or dry – research methods based in statistical physics and computational biology. 

Keywords: biophysics, polymer models, computational biology, chromosomes, mitosis, DNA repair, gene regulation

DARK GENOME IN EARLY MAMMALIAN DEVELOPMENT

Despite the critical importance of 3D genome organization for gene regulation, the mechanisms by which spatial organization of DNA, RNA, and proteins impact nuclear functions post fertilization remains mostly unexplored. In Jachowicz lab we aim to understand the interplay between 3D genome organization and the transcriptome across early mammalian development. We focus on investigating the regulatory role of “dark” genome elements in shaping nuclear functions during early development and use embryonic stem cells and early mouse embryos as model systems. To address our questions, we employ novel, genome-wide technologies that allow us to simultaneously measure 3D nuclear organization and the transcriptome. We combine these methods with systematic functional approaches.

Keywords: early mammalian development, “dark” genome, 3D genome organization, gene expression, single cell omics 

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

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

Macromolecular phase separation in germ cell fate

Cells organize biochemistry into functionally distinct compartments.Canonical cellular compartments are confined within lipid membranes, but recent discoveries suggest that a plethora of cellular compartments form independent of membrane boundaries by liquid-liquid phase separation. We aim to understand how these ‘liquid-like’ compartments assemble and carry out distinct cellular functions. Using multi-disciplinary approaches, we are studying how the canonical liquid-like ‘Nuage’ organelle, conserved in the germline of sexually reproducing animals, contributes to germ cell fate and totipotency.

Keywords: Phase separation, Non-membrane-bound compartments, P granules, nuage, germline cell fate, in vitro reconstitution.