Biology subjects

Heriche, J.-K.

Publications and source records attributed to Heriche, J.-K..

4 recordsLinked to original sources

bioRxiv2017

An experimental and computational framework to build a dynamic protein atlas of human cell division

Essential biological functions, such as mitosis, require tight coordination of hundreds of proteins in space and time. Localization, timing of interactions and changes in cellular structure are all crucial to ensure correct assembly, function and regulation of protein complexes1-4. Live cell imaging can reveal protein distributions and dynamics but experimental and theoretical challenges prevented its use to produce quantitative data and a model of mitosis that comprehensively integrates information and enables analysis of the dynamic interactions between the molecular parts of the mitotic machinery within changing cellular boundaries.\n\nTo address this, we generated a 4D image data-driven, canonical model of the morphological changes during mitotic progression of human cells. We used this model to integrate dynamic 3D concentration data of many fluorescently knocked-in mitotic proteins, imaged by fluorescence correlation spectroscopy-calibrated microscopy5. The approach taken here in the context of the MitoSys consortium to generate a dynamic protein atlas of human cell division is generic. It can be applied to systematically map and mine dynamic protein localization networks that drive cell division in different cell types and can be conceptually transferred to other cellular functions.

systems biology↗

bioRxiv2017

Correlative live and super-resolution imaging reveals the dynamic structure of replication domains

Chromosome organization in higher eukaryotes controls gene expression, DNA replication, and DNA repair. Genome mapping has revealed the functional units of chromatin at the sub-megabase scale as self-interacting regions called topologically associating domains (TADs) and showed they correspond to replication domains (RDs). A quantitative structural and dynamic description of RD behavior in the nucleus is however missing, as visualization of dynamic subdiffraction-sized RDs remains challenging. Using fluorescence labeling of RDs combined with correlative live and super-resolution microscopy in situ, we determined biophysical parameters to characterize the internal organization, spacing and mechanical coupling of RDs. We found that RDs are typically 150 nm in size and contain four co-replicating regions spaced 60 nm apart. Spatially neighboring RDs are spaced 300 nm apart and connected by highly flexible linker regions that couple their motion only below 550 nm. Our pipeline allows a robust quantitative characterization of chromosome structure in situ, and provides important biophysical parameters to understand general principles of chromatin organization.

cell biology↗

bioRxiv2017

Postmitotic Nuclear Pore Assembly Proceeds By Radial Dilation Of Small ER Membrane Openings

The nuclear envelope has to be reformed after mitosis to create viable daughter cells with closed nuclei. How membrane sealing of DNA and assembly of nuclear pore complexes (NPCs) are achieved and coordinated is poorly understood. Here, we reconstructed nuclear membrane topology and structure of assembling NPCs in a correlative three dimensional electron microscopy time-course of dividing human cells. Our quantitative ultrastructural analysis shows that nuclear membranes form from highly fenestrated ER sheets, whose shrinking holes are stabilized and then dilated into NPCs during inner ring complex assembly, forming thousands of transport channels within minutes. This mechanism is fundamentally different from interphase NPC assembly and explains how mitotic cells can rapidly establish a closed nuclear compartment while making it transport-competent at the same time.

cell biology↗

bioRxiv2017

Identifiers for the 21st century:How to design, provision, and reuse persistent identifiers to maximize utility and impact of life science data

In many disciplines, data is highly decentralized across thousands of online databases (repositories, registries, and knowledgebases). Wringing value from such databases depends on the discipline of data science and on the humble bricks and mortar that make integration possible; identifiers are a core component of this integration infrastructure. Drawing on our experience and on work by other groups, we outline ten lessons we have learned about the identifier qualities and best practices that facilitate large-scale data integration. Specifically, we propose actions that identifier practitioners (database providers) should take in the design, provision and reuse of identifiers; we also outline important considerations for those referencing identifiers in various circumstances, including by authors and data generators. While the importance and relevance of each lesson will vary by context, there is a need for increased awareness about how to avoid and manage common identifier problems, especially those related to persistence and web-accessibility/resolvability. We focus strongly on web-based identifiers in the life sciences; however, the principles are broadly relevant to other disciplines.

bioinformatics↗