Humboldt-Universität zu Berlin, Germany
BS: National Autonomous University of Mexico, Mexico City, Mexico
MS: Pierre and Marie Curie University (now Sorbonne University), Paris, France
The protein ASH1 is a member of the Trithorax group of proteins in Drosophila which play important roles maintaining active gene expression states throughout development. Live imaging experiments from my host laboratory have demonstrated the robust binding of ASH1 to mitotic chromosomes in early Drosophila embryos, directing our interest on the role that ASH1 might be playing during this stage of the cell cycle. During my PhD, we will combine molecular biology techniques, single molecule tracking and mathematical modelling to study the contribution of ASH1 on the maintenance of epigenetic memory and/or in cell fate decisions upon the exit of mitosis in Drosophila embryos.
Outside the lab I enjoy hiking, camping, dancing and going to the movies.
Max Planck Institute for Molecular Genetics, Berlin, Germany
BS: Sapienza University of Rome, Italy
MS: Sapienza University of Rome, Italy
Gene expression is tightly regulated, integrating genetic and epigenetic information to produce a spatio-temporal quantitative output. How developmental genes integrate multiple signals to produce the correct expression pattern remains poorly understood. As a model for developmental gene regulation, we investigate the lncRNA Xist, which is essential for X chromosome inactivation (XCI). A number of trans- and cis-regulatory elements act synergistically and cross-talk with the pluripotency network to ensure random female-specific and mono-allelic Xist upregulation at the onset of differentiation. To this end, a two-fold expression difference of X-linked Xist activators must be converted to a binary all-or-nothing response, thus implying a highly non-linear threshold behavior. It remains incompletely understood, however, how such a threshold is established and which molecular players are involved. Addressing this question requires the ability to quantitatively tune expression of each candidate factor and measure the response of the system. In my project I will develop experimental tools to finely tune specific factors and read-out the dose-response curve between candidate regulators and Xist expression with single-cell resolution. Through stochastic mathematical modelling of the regulation of Xist by the perturbed regulator, I will assess which regulatory step is modulated by the regulator and at which level non-linearity arises. In this way we will dissect the effect of multiple factors on XCI in a rigorous mathematical modelling framework.
Outside the lab, I enjoy travelling, binge watching, board games, climbing, cycling, cooking.
John Innes Centre, Norwich, UK
BS: University of Potsdam, Germany
MS: Uppsala University, Sweden
My project aims to gain a better understanding of how the plant flowering repressor FLC (FLOWERING LOCUS C) is transcriptionally regulated in the warm. Previously, it has been shown that the FLC locus is epigenetically shut-down by the Polycomb complex in a digital on/off fashion in response to cold. However, recent data has shown that, before exposure to cold, FLC expression can show a continuously varying (analogue) output. The goal of my project is therefore to understand how analogue and digital mechanisms of regulation can coexist at the same locus.
Outside the lab, I like to be outside in the nature for a hike or climb, I like to cook or go to one of the many pubs in Norwich for a pint.
Niels Bohr Institute, University of Copenhagen, Denmark
BS: Hamburg University, Germany
MS: Humboldt-Universität zu Berlin, Germany
What drives heterochromatin formation and ensures the stability of this silent chromatin state once established? To answer these and related questions, I make use of agent-based stochastic simulations to model the temporospatial process of nucleation and spreading of heterochromatin within a domain in fission yeast. At the moment, the emphasis is on understanding the impact of domain size on heterochromatin establishment. Different models are tested regarding their ability to fit single cell imaging data of different yeast strains where the region of interest has been incrementally expanded. Recent results highlight the importance of the coexistence of long-range and local interactions between nucleosomes. The overall goal is to extract basic mechanistic principles within this epigenetic system and to try to transfer those to mammalian cells.
Outside the lab, I enjoy sports (squash, table tennis, gym), reading (at the moment dystopian\utopian novels, psychology and philosophy) and immersive traveling.
Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
BS: Georg-August-Universität Göttingen, Germany
MS: Ruprecht-Karls-Universität Heidelberg, Germany
The spatiotemporal organization of the genome is tightly linked to transcription, although understanding whether chromosome organization is a cause or a consequence of transcription is still a matter of debate. To help answer this question, a deeper understanding of the spatiotemporal organization of the genome is needed, given that most available studies focus on static measurements, such as fluorescence in situ hybridization (FISH) and chromosome conformation capture (3C) techniques. This project aims to get a better understanding of the dynamics of chromosome structure using live-cell imaging and stochastic modelling. We will establish an ectopic operator array based labeling strategy of endogenous genomic loci and transcribed RNAs, so we can follow up on genomic interactions and their impact on transcriptional output. For example, we will be able to follow the dynamics of enhancer-promoter contacts and their transcriptional output or the impact of proteins involved in the structural maintenance of chromosomes. Resulting data will be interpreted using biophysical models of transcription and chromosome folding to gain a deeper understanding of chromatin dynamics and transcriptional output.
Outside the lab, I enjoy everything related to mountains, e.g. climbing, hiking and skiing. If not there, one can find me cooking with friends or playing board games.
Humboldt-Universität zu Berlin, Germany
BS: University of Tehran, Iran
MS: Royan Institute of Stem Cell Biology and Technology, Tehran, Iran
My project is a cool combination of several areas: epigenetics, gene regulation, developmental biology, and computational biology. I aim to investigate the contribution of DNA sequence to epigenetic regulation by Polycomb/Trithorax group proteins.
During development, a complex multicellular organism originates from a zygote which has to proliferate, differentiate, and make up the whole body. Since the genetic material is identical among the cells, all the specialized cells owe their differences to differential gene expression profiles. In addition to transcription factors, some changes in gene expression during development are accompanied by epigenetic modifications. Epigenetic regulation of gene expression allows the cells to maintain their specialized states.
The Polycomb/Trithorax groups of proteins are chromatin modifier complexes which can work antagonistically on several hundred developmentally important target genes (such as the Hox genes, master transcriptional regulators, and genes involved in signalling and proliferation), to maintain repressed (PcG) or active (TrxG) transcription states. There are cis-regulatory elements in the genome which enable both the PcG and TrxG to bind which are called Polycomb/Trithorax response elements (PRE/TREs). These elements are well characterized in flies, but identifying and understanding mammalian PRE/TREs is one of the most controversial areas in the PcG/TrxG field.
We plan to explore the role of DNA sequence in epigenetic regulation in a systematic genome-wide computational approach in mammalian cells, followed by experimental testing of specific hypotheses.
Outside the lab, I enjoy watching a movie, spending time with friends, traveling, hiking, cooking.
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France
BS: Universidade Federal do ABC, Brazil
MS: Universidade Federal do ABC, Brazil
Gene expression is regulated by transcription factors (TFs) that recognize specific regulatory DNA sequences. The search strategies that TFs use to find their regulatory target sites are key to understand the dynamics of transcriptional regulation. Experiments in-vivo suggest that the 3D structure of chromatin influences the diffusion dynamics of TFs, and that TFs form clusters in the nucleus caused by weak protein-protein interactions, which may help to stabilize DNA binding, recruit RNA polymerase and activate transcription. Moreover, during mitosis chromatin is compacted, nuclear membrane is disrupted and transcription is globally downregulated. However, some TFs are able to remind bound to a subset of their target sites, which is known as mitotic bookmarking. The chromatin structure together with TF clustering influence TF diffusion, and the mitotic bookmarking dynamics constitute part of the dynamics that we want to understand.
Outside the lab, I like knitting (Möbius strips scarfs and beanies, mostly), baking, reading and watching anything sci-fi. I’m a girl with simple tastes.
IRCCS Ospedale San Raffaele, Milan, Italy
Eng: ENSAIA (École Nationale Supérieure D’Agronomie et d’Industrie Alimentaire), France
MS: University of Lorraine, France
Chromosome architecture is known to play an important role in gene regulation, but the mechanisms by which architecture influences gene expression are still an open question. Critically, classical biochemistry methods such as Hi-C or ChIP-seq don’t allow us to probe the dynamics of the interplay between transcription factors and chromatin.
We use live-cell imaging to get around this limitation, by combining single-molecule tracking and super-resolution imaging of chromatin to characterize the effect of chromatin architecture on the target search mechanism of transcription factors. We investigate this in the context of oncogene-induced senescence, an attractive model for its specific disruption of chromatin architecture and associated transcription program. We combine single-molecule tracking with extensive Monte-Carlo simulation that allow us to distinguish between competing underlying explanations of the experimental data.
Outside the lab, I like to read, draw and write. Usually in a less laconic style, and mostly in science-fiction, although I like to vary my pleasures.
Max Delbrück Center for Molecular Medicine, Berlin, Germany
BS: Gettysburg College, Pennsylvania, USA
J. William Fulbright Research Fellowship MDC Berlin, Germany
In the developing mouse embryo, the expression patterns of cell-fate determining transcription factors are known to be regulated through tissue- and stage-specific chromatin contacts between enhancer and promoter sequences. However, the mechanisms by which chromatin contacts drive cell fate decisions remains poorly studied. To interrogate this, the mouse embryo will be used as a model system to produce genome architecture mapping (GAM) datasets. Specifically, the transition between embryonic day 3.5 and 4.5 will be investigated as this transition is critical for establishing pluripotency in the embryo.
Outside the lab, I enjoy rock climbing, reading, and going on hikes with my dog.
University of Oxford, UK
BS: UCLouvain, Belgium
MS: UCLouvain, Belgium
I am working on understanding how metabolism and chromatin regulation can impact gene expression. For this project, we are aiming to derive a stochastic mathematical model describing relationships and determining cause and effect between higher order structures of chromatin and cells phenotype. Combining quantitative experiments with predictive theoretical models is our main objective. To do so, we will use the budding yeast Saccharomyces cerevisiae as model organism and the temporal resolution of the Yeast Metabolic cycle (YMC) as model system. We will study gene expression using methods such as RNA-FISH and look at the higher order structures in chromatin by using DNA-FISH and chromosome conformation capture (3C) in synchronised yeast cells with different metabolic and chromatin states.
Outside the lab, I like to scuba-dive or hike as much as I can. This comes back to my love for Nature and Wildlife. I also enjoy contemporary dance, listening to music or reading a good book. Discovering British writers such as Terry Pratchett was one of the highlights of the beginning of my journey in the UK!
University of Naples Federico II, Naples, Italy
BS – MS: Indian Institute of Science Education and Research, Pune, India
My research project aims to understand chromatin 3D organisation and its underlying physical mechanisms. The plan is to combine Statistical Physics, polymer models, computer simulations and epigenomics high-throughput data analysis, including genome architecture mapping (GAM), Hi-C and other chromatin contact data, as well as epigenomics and disease related databases. I expect, in particular, to understand general mechanisms of chromosome folding and specific molecular factors acting in model loci linked to human phenotypes and embryo development.
Outside the lab, I like to listen to music, reading, watching movies and series, and walking around aimlessly.
BS: University of Oviedo, Oviedo, Spain
MS: Autonomous University of Madrid, Madrid, Spain
My project involves the development of a whole workflow for single-cell small non coding RNA-sequencing basing on the adaptation of a previously developed library preparation method for small RNA-sequencing. The development of this technology is relevant because small non-coding RNAs are involved in maintaining cell transcriptional profiles stability and subsequently in defining cell identity. They also play key roles in enabling an adpative cell response to the changing environmental conditions. Since bulk RNA-seq approaches can mask lowly expressed transcripts that may be biologically relevant, one of the main advantages of scaling RNA-seq to the single-cell level is to look at each cell non-coding transcriptome heterogeneity and abundance of transcripts and hopefully identifying new cell types, developmental stages or outlier cells, among other applications. The development of this technology also entails a dry-lab approach carried out by ESR14 in order to develop a software to process and analyze the sequencing data and to contribute to the experimental design.
Outside the lab, I enjoy travelling, photography, drawing, hiking and spending time with my friends.
BS: Pompeu Fabra University, Barcelona, Spain
MS: University of Barcelona and Polytechnic University of Catalonia, Barcelona, Spain
My project focuses on the development of an accurate methodology to quantify and analyze short non-coding RNA (sncRNA) expression from single-cell transcriptome sequencing experiments. Ultimately, my work aims to help the scientific community to gain new insights of the functions and roles of sncRNA within the cell by providing with a novel tool that is currently not available in the single-cell RNAseq field. For this, I team up with ESR 13 to properly address both wet-lab protocol development and data processing of the targeted methodology, being myself the one who focuses on the data processing and analysis challenges. This new type of NGS data entails various difficulties. On one hand, the challenge of assigning and quantifying very short non coding RNA reads that can be originated from multiple genome loci and from transcripts that are not discovered yet. On the other hand, addressing single-cell RNAseq analysis challenges as the identification of technical and biological covariates such as batch, dropout and cell cycle effects based uniquely on the non-coding transcriptome.
Outside the lab, I like meeting people and exploring new places. I especially like going trekking and travelling on long road trips. I also spend some time each week singing with my guitar.
University of Oxford, UK
Eng: ETH Zürich, Switzerland
Sequencing technology have led to the development of many high-resolution methodologies to follow genome activity and gene expression. Jane Mellor’s lab is leading in applying and developing such methods as TT-seq, NETseq/mNETseq and recently SNUseq to capture nascent RNA transcript and the density of RNA polymerase across the yeast genome. Experimental data was already used in the lab to develop stochastic Markov models for the polymerase tracking at the 3’ end. These numerical models are verified with experimental data on mutations and transcription factors. Based on new next generation sequencing technics with higher resolution the 5’ end is approached with the goal to develop a unitary global model along RNA transcription. On top, analytical regulatory feedback models will be applied to capture specific transcription activities and compared with the numerical model and experiment results. The combination of numerical and analytical methods with new sequencing technology allows us to understand RNA transcription beyond yeast and biological model organisms.
The Giorgetti Lab explores the biophysical mechanisms that link chromosome conformation and longrange transcriptional regulation in mouse embryonic stem cells (ESC) and differentiated derivatives, using molecular biology, genetic engineering, single-cell experiments and physical modelling.
The Howard Lab uses mathematical modelling and theory to understand complex mechanistic cell biological problems. The group works with experimental scientists who provide data for modelling in, for example, epigenetic regulation or cell size control. Mathematical modelling of these problems provides clues as to what is possible biologically.
The Mazza group focuses on the development and the application of advanced fluorescence microscopy methods to detect, track and quantify the behaviour of individual molecules in living-cells, with a specific focus on the kinetic behaviour of cancer-related transcription factors.
The Mellor Lab uses the budding yeast S. cerevisiae, mammalian cells and mathematical modelling in which to study how transcription, non-coding RNAs, higher order structures in chromatin, and histone modifications influence the response to changes in nutrient availability, metabolic state and ageing.
The Molina Lab contributed innovatively to investigate the stochasticity of transcription in mammalian cells by uncovering fundamental kinetic properties of gene reactivation. Our work lies at the interface between bioinformatics and biophysics to develop mechanistic models of eukaryotic gene regulation by integrating genome-wide data and live-cell imaging.
The Nicodemi group works on the Physics of Complex Systems and its applications to Molecular Biology. The group pioneered the understanding of the complex three-dimensional architecture of the human genome and its links with gene regulation by combining their Statistical Physics description and computer simulations.
The Pombo Lab is interested in understanding the interplay between gene regulation and genome architecture, to define principles of genome function. Our long-term strategy for unravelling the principles of genome function with new developments in molecular biology, epigenetics, nuclear imaging, proteomics and genetics.
Our research focuses on the probabilistic and statistical modelling of genetic, genomic, transcriptomic and epigenetic phenomena. We employ machine learning techniques to make predictions of genome-wide Polycomb/Trithorax targeting in Drosophila and in human/mouse and to uncover the underlying architecture of recruiting DNA elements.
Our laboratory uses a combination of quantitative live imaging, mathematical modelling, computational approaches and molecular and developmental biology in Drosophila and in mammalian cell culture to understand the interaction of the Polycomb and Trithorax proteins with their chromatin targets and with-non coding RNAs.
Diagenode is a leading global provider of complete solutions for epigenetics research, biological sample preparation, and diagnostics assays based in Liege, Belgium and NJ, USA. The company has developed a comprehensive approach to gain new insights into epigenetics studies.
The overall goal of our research is to elucidate the regulatory principles employed by gene-regulatory networks to reliably control the transition of embryonic stem cells to further differentiated cell types. We combine mathematical modelling with microscopy, genomics and genome engineering techniques to investigate the molecular mechanisms that govern X-inactivation.
The Sneppen Lab pioneered mathematical modelling and theory to understand nucleosome-mediated epigenetic memory. The group works closely with experimentalists investigating diverse models of life, including epigenetic regulation of bistable systems.