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Precision Surface Microtopography Regulates Cell Fate via Changes to Actomyosin Contractility and Nuclear Architecture

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Structural basis of BAK sequestration by MCL-1 in apoptosis

Alexander Myasnikov, Emiko Uchikawa

Apoptosis controls cell fate, ensuring tissue homeostasis and promoting disease when dysregulated. The rate-limiting step in apoptosis is mitochondrial poration by the effector B cell lymphoma 2 (BCL-2) family proteins BAK and BAX, which are activated by i ...

2025

Revealing chromatin-specific functions of histone deacylases

Beat Fierz, Carlos Moreno Yruela

Histone deacylases are erasers of Nε-acyl-lysine post-translational modifications and have been targeted for decades for the treatment of cancer, neurodegeneration and other disorders. Due to their relatively promiscuous activity on peptide substrates in v ...

2024

Mapping of centriolar proteins onto the post-embryonic lineage of C. elegans

Pierre Gönczy, Nils Kalbfuss

Centrioles, together with the surrounding peri-centriolar material (PCM), constitute the centrosome, a major microtubule-organizing center of animal cells. Despite being critical in many cells for signaling, motility and division, centrioles can be elimina ...

ACADEMIC PRESS INC ELSEVIER SCIENCE2023

cgNA+: A sequence-dependent coarse-grain model of double-stranded nucleic acids

Rahul Sharma

DNA mechanics plays a crucial role in many biological processes, including nucleosome positioning and protein-DNA interactions. It is believed that nature employs epigenetic modifications in DNA to further regulate gene expression. Moreover, double-strande ...

EPFL2023

Cooperation between bHLH transcription factors and histones for DNA access

Beat Fierz, Kristina Makasheva

The basic helix-loop-helix (bHLH) family of transcription factors recognizes DNA motifs known as E-boxes (CANNTG) and includes 108 members(1). Here we investigate how chromatinized E-boxes are engaged by two structurally diverse bHLH proteins: the proto-on ...

NATURE PORTFOLIO2023

Metabolic dependencies of metastasis-initiating cells in female breast cancer

Jörg Hülsken, Albert Santamaria Martinez, Candice Megan T Young, Pierre Vincent Dessen, Angela Madurga Alonso, Laurent Nam Ky Beziaud

Understanding the mechanisms that enable cancer cells to metastasize is essential in preventing cancer progression. Here we examine the metabolic adaptations of metastasis-initiating cells (MICs) in female breast cancer and how those shape their metastatic ...

Nature Portfolio2023

Dissecting centriole fate in C. elegans development

Nils Kalbfuss

The presence of centrioles is critical for fundamental cell and developmental processes, including polarity, migration and division. Although centrioles are present in most proliferating cells, they are thought to vanish after cell cycle exit in some diffe ...

EPFL2022

New approaches to uncover the minimally functional hematopoietic niche using the adipocytic differentiation axis: pharmacological modulation and adrenal niche induction

Frédérica Schyrr

Hematopoietic Stem and Progenitor Cells (HSPCs) reside in their niche, a structure that regulates the balance of cellular quiescence, self-renewal and commitment towards differentiated cells. This highly plastic niche is formed by several cellular players, ...

EPFL2022

Tcf1 is essential for initiation of oncogenic Notch1-driven chromatin topology in T-ALL

Christelle Dubey, Freddy Radtke, Ute Koch, Nadine Fournier, Mateusz Waldemar Antoszewski, Marianne Nkosi, Tara Kimberly Sugrue

NOTCH1 is a well-established lineage specifier for T cells and among the most frequently mutated genes throughout all subclasses of T cell acute lymphoblastic leukemia (T-ALL). How oncogenic NOTCH1 signaling launches a leukemia-prone chromatin landscape du ...

AMER SOC HEMATOLOGY2022

Microarrayed human bone marrow organoids for modeling blood stem cell dynamics

Matthias Lütolf, Nathalie Brandenberg, Romain Guiet, Sonja Giger, Moritz Hofer

In many leukemia patients, a poor prognosis is attributed either to the development of chemotherapy resistance by leukemic stem cells (LSCs) or to the inefficient engraftment of transplanted hematopoietic stem/progenitor cells (HSPCs) into the bone marrow ...

AIP Publishing2022

Pulchelloid A, a sesquiterpene lactone from the Canadian prairie plant Gaillardia aristata inhibits mitosis in human cells

Pierre Gönczy, Georgios Hatzopoulos, Tatiana Favez

Background The Canadian prairie ecosystem presents a rich source of natural products from plants that are subjected to herbivory by grazing mammals. This type of ecological competition may contribute to the production of natural products of interest in cel ...

SPRINGER2021

In vitro modeling of early mouse development

Mehmet Ugur Girgin

Previous attempts to recapitulate embryogenesis in a developmentally relevant context started with aggregates composed of a few thousand ESCs, termed embryoid bodies (EB), that upon induction of differentiation reveal a surprising level of autonomous cell ...

EPFL2020

A complex regulatory landscape involved in the development of mammalian external genitals

Denis Duboule, Lucille Delisle, Christopher Chase Bolt

Developmental genes are often controlled by large regulatory landscapes matching topologically associating domains (TADs). In various contexts, the associated chromatin backbone is modified by specific enhancer-enhancer and enhancer-promoter interactions. ...

2020

A Tale of Two Tumors: Unraveling the Complexities of Epigenetic Dysregulation in Cancer

Maria Christine Donaldson

Epigenetics plays an important role in cancer development and progression. Cancer cells hijack the epigenome by modifying the histone protein units responsible for packaging DNA, or by modifying the DNA itself, resulting in changes to chromatin topology an ...

EPFL2019

Gene control with a "twist": Exploring the dynamic chromatin landscape Gene control with a "twist": Exploring the dynamic chromatin landscape

Beat Fierz

SPRINGER2019

Live imaging screen reveals that TYRO3 and GAK ensure accurate spindle positioning in human cells

Pierre Gönczy, Coralie Busso, Benita Wolf

Proper spindle positioning is crucial for spatial cell division control. Spindle positioning in human cells relies on a ternary complex comprising G alpha i1-3, LGN and NuMA, which anchors dynein at the cell cortex, thus enabling pulling forces to be exert ...

Springer2019

Casein kinase 2 mediated phosphorylation of Spt6 modulates histone dynamics and regulates spurious transcription

Eric Paquet

CK2 is an essential protein kinase implicated in various cellular processes. In this study, we address a potential role of this kinase in chromatin modulations associated with transcription. We found that CK2 depletion from yeast cells leads to replication ...

OXFORD UNIV PRESS2018

The chromatin remodeling factor ISW-1 integrates organismal responses against nuclear and mitochondrial stress

Johan Auwerx, Maroun Bou Sleiman

Age-associated changes in chromatin structure have a major impact on organismal longevity. Despite being a central part of the ageing process, the organismal responses to the changes in chromatin organization remain unclear. Here we show that moderate dist ...

Nature Research2017

Genomic targets and molecular partners of the chromatin regulator KAP1

Annamaria Kauzlaric

KAP1 is an enigmatic regulatory protein, first described some twenty years ago, shown to be involved in multiple and diverse cellular functions. Specifically, it mediates tasks critical to cell growth and differentiation, pluripotency, apoptosis, gene sile ...

EPFL2017

Dynamic Chromatin Regulation from a Single Molecule Perspective

Beat Fierz

Chromatin regulatory processes, like all biological reactions, are dynamic and stochastic in nature but can give rise to stable and inheritable changes in gene expression patterns. A molecular understanding of those processes is key for fundamental biologi ...

American Chemical Society2016