Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

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. In mammals, regeneration is rare, limited to skin, liver, and toes. 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 fruit fly, Drosophila melanogaster, has for the last century been fundamental to the study of genetics. It is used in many areas of research as the model organism of choice, as it provides the ability to study genetics in the laboratory and apply findings to human genetics. Its use as a model is due to two factors: First, its genetic code can be relatively easily manipulated in the laboratory and this coupled with a short life cycle, provides a means by which a gene or pathway function can be rapidly studied. Secondly, the vast majority of the fundamental biochemical mechanisms and pathways are conserved between fly and humans. Indeed, 75% of the genes that cause human disease are found in fly and, thus, the data collected in the fly can be used to provide insights into the same processes within humans. The emergence of a new technology, single cell RNA sequencing (scRNA-seq), has provided information as to which genes are switched on or most active from a single cell. Within the fly community this provides the ability to quickly map clusters of cells and cell types to the whole anatomy and link this to both phenotype and function. The increasing number of scRNA-seq datasets from different species has resulted in the development of the Single Cell Expression Atlas (scEA). This is a web portal which enables users to more easily visualise and interpret this data. It is anticipated that the level of fly single cell data will increase from 10 datasets to ~100 in 2020 and further two-fold increase in 2021. Key to the scientific exploitation of this data will be the ability of users to not only effectively analyse the fly data but also to examine the interconnections between fly data and human or mouse datasets. In this project we will provide the means by which fly datasets can be easily interpreted and also linked to mouse and human datasets via scEA. The scEA currently hosts scRNA-seq data for over 500K assays and this includes data for the Human Cell Atlas (HCA) and Mouse Cell Atlas (MCA), amongst others. This project will enable analysis pipelines to be developed to combine the available and emerging datasets, alongside the necessary computational infrastructure to host the Fly Cell Atlas (FCA) datasets. ScEA will provide users with an easy to navigate web service with exploratory querying capability, in addition to data download capabilities for further data analysis. The service will be fully integrated with the established fly resources, Flybase, Virtual Fly Brain and the Drosophila Resources at Harvard University. This project will also develop a process for annotation of the datasets. This annotation step adds additional scientific information to the data which provides the user with a greater level of biological understanding and so aids the interpretation and analysis. This annotation will expand on the existing FlyBase anatomy ontology which is a structure of controlled vocabularies used to describe the anatomy of the fly this will ensure that there is full compatibility across new and existing resources. The scEA will develop and provide the means by which the data can be easily visualised and mined for cell types, while also providing the fly community with the ability to contribute their scientific expertise to the annotation. The scEA user interface will be further developed to provide a greater level of cross species query ability as the resulting FCA will be linked within scEA to the HCA, MCA and any further datasets enabling cross species comparisons which will aid in the discovery of novel biological insights. This project aims to provide the fly community with practical solutions for connecting, re-using and reanalysing datasets and so will close the gap in translating biological discoveries in model organisms, such as the fruit fly, to humans and vice versa. This project will make the results of this comparative analysis rapidly available to the growing user community.

All cells contain a complete copy of the organism's DNA, the genetic blueprint of life, packaged into discrete units called chromosomes. Since new cells need a copy of the genetic material, the chromosomes must be completely and accurately replicated before the cell can divide. This requires the process of DNA replication to start at thousands of sites across the chromosomes - called DNA replication initiation sites. Our project aims to determine the location of replication initiation sites in human cells. This is important because the location and distribution of replication initiation sites have been implicated in causing human diseases such as cancer. It has been challenging to identify DNA replication initiation sites in human cells, because there is a lot of variability between cells. To date, most experiments have used the average from millions of cells, but this hides the variability between cells. We have developed a novel technology that identifies DNA replication initiation sites on thousands of single molecules that each originated in a single cell. Our approach can also identify specific sequences that are challenging to copy. This will allow us to test the hypothesis that some sites, thought to be involved in replication initiation, in fact are sites that impede DNA replication. Distinguishing between sites that initiate versus impede DNA replication will be crucial in understanding the causes of genetic instability that underlie some human diseases.

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.