15 Phd Positions In Decoding Transcriptional Regulation In Regeneration By Advanced Genomics An[...]

15 PhD positions in Decoding Transcriptional Regulation in Regeneration by Advanced Genomics and Computational tools (funded by the DANIO-ReCODE MSCA 2023 Doctoral Network)The principal objective of DANIO-ReCODE is to provide world-class doctoral training to a new generation of early-career researchers interested in understanding the complex and multilayered process of tissue regeneration.
DANIO-ReCODE will combine the multidisciplinary expertise of 15 research laboratories at renowned EU and UK scientific institutions to unravel the regulatory mechanisms of heart, brain, and eye regeneration by employing the unique and highly tractable zebrafish model system.
Unlike humans, teleosts can repair damaged tissues or even regrow entire appendages.
Regenerative medicine, however, promises to restore tissue function via the use of stem cells, tissue engineering, and the production of artificial organs, with its importance being recognised as one of the EU strategic missions.
A fundamental gap of knowledge is the understanding of the shared and distinct regulatory mechanisms defining regeneration in highly regenerative species and those with lower regeneration potential such as mammals.
Since the vertebrate gene complement is highly conserved, applying the knowledge of regeneration mechanisms from non-mammalian models such as zebrafish could identify genetic underpinnings, which when manipulated in mammals, could strongly boost the mammalian regenerative potential.
DANIO-ReCODE will thus nurture a cohort of exceptional doctoral candidates and turn them into interdisciplinary experts in computational and developmental biology, providing comprehensive training that spans experimental work, bioinformatics, visualisation, and industry applications.
Through the integration of state-of-the-art genomics, computational, and data visualisation techniques, DANIO-ReCODE will result in an enhanced understanding of molecular determinants implicated in vertebrate regenerative processes while providing new avenues for the repair or replacement of damaged or diseased tissues and organs.The list of individual positions and lead contacts is provided below:DC1: Cis-regulation during in vivo and in vitro organ developmentPartner: Spanish National Research Council (Andalusian Centre for Developmental Biology, Seville, Spain)Regenerative medicine relies heavily on organoid research to be able to accurately recapitulate organ development in vitro and to ultimately use such organs to replace diseased or ageing ones.
Reproducible morphology is currently the main landmark used to rank organoid formation; however, the epigenetic landscape of the organ representing underlying genomic activity states, should also be reproduced in order to obtain representative and functional organoid differentiation.
The doctoral candidate will tackle this question by comparing the profiles of regulatory elements in vivo (embryo) versus in vitro, in zebrafish eye organoids, by performing single cell multiome, histone modification, and base-resolution DNA methylome profiling.
Overall, the candidate will integrate these data to identify a core set of gene-regulatory regions that drive optimal eye development in vitro.DC2: Identification of cis-regulatory elements that support optimal eye organoid morphogenesisPartner: Spanish National Research Council (Andalusian Centre for Developmental Biology, Seville, Spain)Differentiation, regeneration and other morphogenetic processes crucially depend on the mechanical forces acting on differentiating cells.
The doctoral candidate will investigate how the mechanical state of zebrafish eye organoids translates into changes in epigenetic patterning and find which matrix compositions better support the in vivo epigenetic state.
The candidate will first modify the tensional forces of eye organoids by: 1) modification of YAP signalling, and 2) the use of ferrofluidic droplets to alter the mechanical integrity of the tissue.
The changes in epigenetic signatures in response to these perturbations will be analysed by RNA-seq, ATAC-seq and WGBS to identify specific gene regulatory regions of the chromatin that adapt to changes in those cell-extrinsic mechanical inputs.
The candidate will use these mechanically sensitive gene regulatory regions to explore which matrices or alternative synthetic hydrogels mimic better the in vivo gene-regulatory state.
This approach will permit for the efficient selection of settings that support optimal organoid morphogenesis.DC4: Characterisation of cis-regulatory networks in cardiac muscle de- and re-differentiation in heart regenerationDuring heart regeneration, dedifferentiated and newly proliferated cardiomyocytes re-differentiate and integrate with existing heart muscle cells.
A key question is whether the same genetic programs, including cis-regulatory elements (CREs) that control cardiac muscle differentiation during development, are reactivated in the heart regeneration process.
In this project, the doctoral candidate will generate new datasets and analyze existing ones from bulk and single-cell RNA sequencing (scRNA-seq) and ATAC-seq of isolated cardiomyocytes from developing zebrafish embryos and regenerating adult zebrafish hearts.
The candidate will also explore and compare the CREs and downstream transcriptional targets activated in developing versus regenerating cardiomyocytes using integrative genomics and imaging techniques.DC5: Promoter architecture and usage during zebrafish, axolotl, and mouse regenerative neurogenesisThis position focuses on conducting cutting-edge research in comparative genomics and computational biology to investigate promoter architecture during adult and regenerative neurogenesis in zebrafish, mice, and axolotl.
The candidate will use advanced ML techniques and AI to interpret CAGE-seq data on the regulatory mechanisms involved in gene expression during neurogenesis.
The goal is to uncover the commonalities and differences in these processes across species, contributing to a deeper understanding of vertebrate regenerative capabilities.DC6: Novel approaches to integrate genomic information from model organisms into human regulatory landscapesThis position focuses on integrating multiomics data from model organisms into human disease and phenotype contexts.
The researcher will develop innovative visualization methods to map single-cell, DNA methylation, and other genomic datasets against known human disease and phenotype information.
They will enhance existing web resources by adding regulatory features related to development and regeneration, providing a human-centric perspective.
Additionally, the researcher will generate and prioritize novel hypotheses regarding regulatory elements involved in human diseases, subsequently validated in collaboration with experimental partners.
The work will bridge insights from model organisms to human health, driving forward our understanding of disease mechanisms.DC7: Identifying the gene regulatory code for regenerationPartner: Institute of Molecular Biotechnology, Vienna, AustriaAxolotls have the remarkable ability to regenerate multiple body parts.
Interestingly, we have observed some genes that are commonly up regulated across different regenerating organs.
We will use advanced chromatin profiling and bioinformatics methods, including comparison across species to identify the conserved and non-conserved gene regulatory elements that initiate regeneration.DC8: Deciphering molecular programs regulating the reversible quiescence of mammalian neural stem cellsOur lab is offering a PhD position for a project aimed at identifying gene expression programs involved in the transitions of neural stem cells from quiescence to activation and back in the mouse brain.
This project will employ advanced techniques such as Single-cell Nucleosome, Methylome and Transcriptome (scNMT-seq) to characterize chromatin accessibility, methylome and transcriptome at the single cell level in neural stem cells at different states of activation.
The ultimate goal is to identify molecular mechanisms and gene expression programs involved in the regulation of reversible quiescence.DC9: Conversational AI for exploring complex data in tissue regeneration researchPartner: University of Ljubljana, Ljubljana, SloveniaIn this PhD project, you will develop an AI-powered chatbot to transform how researchers interact with complex, heterogeneous data in regenerative biology.
You will work on creating a literature-focused chatbot that integrates scientific references, build tools to chat about project-specific data, such as gene expression patterns, and design solutions for integrating diverse data sources, including literature, datasets, and biological knowledge bases, into a cohesive, interactive platform.
Your work will empower biologists studying tissue regeneration, such as heart, brain, and eye regeneration, by providing them with faster access to data, more efficient generation of insights, and advanced visualization tools, ultimately enhancing their ability to unravel the complex mechanisms underlying regenerative processes.DC11: Novel solutions for combining multi-omics embeddings and regulatory network visualisationsPartner: Johannes Kepler University Linz, Linz, AustriaThis project aims at developing novel, hybrid embedding algorithms to visualize regulatory network data as low-dimensional representations.
These algorithms should combine the information from high-dimensional data attributes and from topological network relationships.
Additionally, the project aims at designing visual enrichment techniques and interactions that help users interpret these low-dimensional representations effectively.DC12: Annotation, characterisation, and conservation of 3D chromatin topology in telencephalon injuryPartner: University of Birmingham, Birmingham, UKThe aim of this position is to understand the role of chromatin topology in the regeneration of injured telencephalon in adult zebrafish.
The doctoral candidate will analyse Hi-C and PCHi-C data in injured telencephalon in adult zebrafish to identify regeneration specific chromatin topology.
She/he will use data integration methods for Hi-C, single-cell epigenomics and CAGE-seq data to characterise the chromatin topology around genes implicated in regeneration focusing on cis-regulatory interactions.
The candidate will also use comparative analysis of chromatin topology between zebrafish and mouse, to study the conservation of chromatin topology around genes implicated in tissue regeneration.DC13: Multi-omic characterisation of transcription initiation regulation in development and injury responsePartner: University of Birmingham, Birmingham, UKIn this project the student will work in a team formed by an international, interdisciplinary consortium to explore the transcription regulatory landscape and codes of transcription initiation variation in developmental and neural injury models.
The student will learn developmental gene manipulation in zebrafish, single cell genomics technologies, computational analyses of multi-omic datasets to study promoter level regulation of normal development and injury response.Partner: Imperial College London, London, UKThis project explores the regulatory genomics underlying vertebrate regeneration, aiming to uncover shared and distinct mechanisms with embryonic development.
Through a comparative approach, the project will investigate highly conserved regulatory features, integrating experimental data across species to generate and test hypotheses on the fundamental properties of gene regulation in embryonic development and its evolution.
The student will engage in cutting-edge research combining computational genomics, statistics, and machine learning, with opportunities for cross-disciplinary training within a collaborative international network.
This work will contribute to creating an atlas of key regulatory genes and pathways involved in regeneration and development, with the potential to revolutionise our understanding of these biological processes.DC15: Cross-species cell atlases for regenerationThis project will aim to develop comprehensive cell atlases of regeneration in three different species, zebrafish, mouse and axolotl.
The doctoral candidate will integrate single cell transcriptomic as well as epigenetic data to assemble the atlases within each species and to compare cell types and regulatory processes across species.
The project will use data generated by our partners within the DANIO-ReCODE doctoral network, as well as publicly available datasets.
It will be fully computational and will aim to further advance our methods in cross-species comparisons of transcriptomics data sets, as well as develop new methods for identifying conserved or divergent key cell types and regulatory programmes across species.
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