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

MOLECULAR DETERMINANTS OF BIOLOGICAL IDIOSYNCRASY

| What makes individuals, populations and ultimately species different from each other? What are the genetic and molecular mechanisms responsible for the myriad of adaptations present in nature? The primary goal of the Burga lab is to understand at the molecular level the forces driving the evolution of complex traits with a particular emphasis on the contribution of epistatic interactions (genetic modifiers) and genomic conflict (selfish elements). To do so, we apply a multidisciplinary approach that combines our expertise in quantitative genetics, genomics and developmental biology in systems ranging from nematodes to vertebrates.

Keywords: genomics, selfish elements, speciation, hybrids, complex traits

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

CHROMOSOME STRUCTURE AND DYNAMICS

| Chromosomes not only store and protect genetic information, but they also facilitate the copying and transmission of an organism’s blueprint to daughter cells at cell division. This process of DNA replication and segregation involves a series of highly coordinated steps that result in physical changes to chromosome shape. Our lab is investigating this dynamic chromosome reorganization – and the molecular factors involved – during the cell cycle. We use a combination of techniques from genome imaging and engineering to computational biology to in vitro reconstitution assays to understand chromosome structure and reorganization events in human cells, and the implications for gene expression, DNA repair, and chromosome segregation. As we characterize factors responsible for various steps, we will also better understand how chromosomes, the cytoskeleton, and membranes interact to form functional interphase cells at the end of mitosis.

Keywords: chromosomes, mitosis, advanced microscopy, genomics, biophysics

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

MECHANISMS OF PLASTICITY AFTER BRAIN INJURY

| Formerly perceived as a hardwired rigid structure, constrained by stable networks, the adult mammalian brain is now known to be malleable, in particular, in the aftermath of an injury. The Grade lab investigates the fundamental biological principles of neural circuit plasticity upon brain injury or disease, using mouse as a mammalian model system. We take a system-wide approach to allow an understanding of complex interactions at the neural networks level, within the biological system. Our goal is to uncover the magnitude and mechanistic basis of induced plasticity which will illuminate potential intervention approaches for brain injury or neurodegenerative conditions.

Keywords: brain injury, connectivity, neural networks, circuit plasticity, remodeling

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 

BRAIN DEVELOPMENT AND DISEASE

| The human brain is the most complex of all organs. In the Knoblich lab, we are fascinated by the mechanisms behind its assembly and function, and study them using a unique combination of model organisms ranging from insects to humans. So far, analysis of the simple nervous system of the fruit fly, Drosophila melanogaster, has allowed us to understand how neural stem cells divide and differentiate to generate diverse neurons, as well as how defects in these processes can cause tumor formation. To analyze these events directly in human brain tissue, we have recently developed the cerebral organoid system that generates human fetal brain-like tissue from pluripotent stem cells in vitro. This system allows us, in collaboration with clinical research groups, to derive three-dimensional culture models for neuro-psychiatric disorders and analyze their developmental origin in a deeply mechanistic manner. Our analysis of brain development will illuminate the causes behind, and potential therapies for various neurodevelopmental and neurological disorders.

Keywords: stem cells, brain, organoids, neurogenesis, neurons

MOLECULAR CONTROL OF HUMAN CARDIOGENESIS

| The heart is the first organ that forms in humans but how molecules instruct cells to form such a fascinating structure is not understood. The aim of the Mendjan lab is to recapitulate human heart development in vitro, discover the molecular mechanisms that drive cardiac self-organization, and how this fails in congenital heart disease. Our approach is to use human pluripotent stem cell differentiation into self-organizing heart organoids called "cardioids" to decipher the molecular control of cardiac organogenesis, and of associated disorders. 

Keywords: Heart development, human pluripotent stem cells, self-organization, cardiac organoids, cardioids

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

LABORATORY FOR BLASTOID DEVELOPMENT AND IMPLANTATION

| Throughout evolution, embryos developed efficient ways of emanating from stem cells. The Rivron lab recreates embryonic development using stem cells in a dish to better understand the encoded principles of self-organization. We use blastocysts and self-organizing models formed from stem cells, that we termed blastoids, to investigate how and why the flow of information between cells regulates spatio-temporal patterning and cell-fate decision making. This requires to consider blastocysts as complex systems from the viewpoint of physicists and engineers. We are a team of stem cell biologists, geneticists, synthetic biologists and engineers whose research is grounded in technological and computational approaches (e.g., microsystems, single cell sequencing, three-dimensional high content imaging) and collaborating with physicists.

Keywords: blastoids, stem cells, self-organisation

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.

REGULATION OF NEURAL STEM CELL QUIESCENCE

| Adult neural stem cells (NSCs) generate neurons throughout life which integrate into existing circuits modulating memory and behavior. A key feature of adult NSCs is that most are in an inactive state (quiescence) until receiving activation stimuli. Since adult NSCs have a limited ability to self-renew, their activation is coupled with exhaustion, explaining the decline in neurogenesis with age. We investigate the mechanisms driving the transition of adult NSCs between proliferation and quiescence to devise strategies to prevent their exhaustion. We use in vivo and in vitro tools to understand how extrinsic signals, like diet and Insulin/IGF signaling, regulate adult NSC behavior.

Keywords: brain, adult stem cells, quiescence, niche, metabolism, signaling

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