Julius Brennecke

Defending the Genome: Exploring the Molecular Arms Race Between Transposons and Their Hosts

Eukaryotic genomes are not static blueprints but dynamic conflict zones shaped by the ancient struggle between selfish genetic elements and their hosts. Transposable elements are the most prominent invaders, capable of copying and inserting themselves across the genome, disrupting genes and threatening genome stability. Yet, eukaryotes have evolved powerful defence systems to keep these elements in check. As a result, genomes can tolerate vast amounts of transposons, which make up half of the human genome and up to 80% of some plant genomes. Our group investigates the molecular principles of this conflict, focusing on how small RNA-guided genome immune systems silence transposons—and how transposons, in turn, evolve to escape suppression. Notably, this ongoing evolutionary arms race is one of the major drivers of molecular innovations in biology.

Keywords: transposable elements, small RNA biology, PIWI/piRNA pathway, heterochromatin, epigenetics, germline biology

Julius Brennecke Research Group

Alejandro Burga

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

Alejandro Burga Research Group

Daniel Gerlich

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

Daniel Gerlich Research Group

Anton Goloborodko

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

Anton Goloborodko Research Group

Sofia Grade

Plasticity and Repair 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

Sofia Grade Research Group

Joanna Jachowicz

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 

Joanna Jachowicz Research Group

Sven Klumpe

In situ structural biology laboratory

The Klumpe lab develops and applies technologies for in situ structural biology to address questions in germline biology with a special interest in transposable elements. Specifically, we use focused ion beam-scanning electron microscopes (FIB-SEM) to produce cellular thin sections at cryogenic temperatures. In conjunction with high-end transmission electron microscopy (TEM), we can generate three dimensional reconstructions of the cellular interior from these thin sections by cryo-electron tomography. This allows us to study biological macromolecules in their native environment, the inside of a cell, and resolve them in the most favorable cases down to secondary structure elements and potentially even sidechains.

Keywords: In situ structural biology, transposable elements, retrotransposons, Drosophila melanogaster

Sven Klumpe Research Group

Jürgen Knoblich

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

Jürgen Knoblich Research Group

Sasha Mendjan

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

Sasha Mendjan Research Group

Nicolas Rivron

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

Nicolas Rivron Research Group

Kristina Stapornwongkul

Environmental and metabolic regulators of embryonic development

The environment is a key regulator of embryonic development. External conditions, such as nutrients and oxygen levels, influence the metabolic state of cells. In recent years, it has become clear that beyond ATP and building block production, metabolic processes also regulate signalling pathways and chromatin accessibility. This raises the question of metabolism's role in development. Our lab uses stem cell-based in vitro model systems to investigate the tissue scale organisation of metabolic processes and their impact on developmental processes. Our aim is to uncover the underlying principles by which metabolism regulates tissue patterning and morphogenesis.

Keywords: embryonic development, stem cell-based in vitro model systems, nutritional environment, metabolism, bioenergetics

Kristina Stapornwongkul Research Group

Elly Tanaka
Scientific Director

Molecular Mechanisms of Vertebrate Regeneration

The Tanaka lab seeks to understand the cellular mechanisms underlying salamander limb and spinal cord regeneration as a model for how successful regeneration occurs in a vertebrate. This model acts as a starting point to rigorously investigate how mammals such as mice have lost regeneration capabilities over evolution. In addition, these studies act as a springboard to design novel strategies for regenerating or replacing mammalian tissues. Toward that end the Tanaka lab has engineered three-dimensional spinal cord tissue from mouse embryonic stem cells and retinal pigment epithelia from human embryonic stem cells.

Keywords: limb regeneration, spinal cord regeneration, stem cells, axolotl

Elly Tanaka Research Group

Noelia Urbán

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

Noelia Urbán Research Group

Josef Penninger

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

Josef Penninger Research Group

Stefan Ameres

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

Stefan Ameres Research Group

Daniela Pollak

Internal and external factors that shape behaviour

The Pollak lab aims to uncover the mechanistic interface that modulates the bidirectional interdependence between internal and external factors that jointly determine the intricacy of behavioral outputs in health and disease.

Keywords: mouse model, behavioral neuroscience, circuitry neuroscience, early-life experience, hypothalamus, brain plasticity

Daniela Pollak Research Group