Award details

FlyAtlas2: a definitive, expanded NGS expression resource for the Drosophila community and beyond

Reference	BB/K019953/1
Principal Investigator / Supervisor	Professor Julian Dow
Co-Investigators / Co-Supervisors	Professor Shireen Davies
Institution	University of Glasgow
Department	College of Medical, Veterinary, Life Sci
Funding type	Research
Value (£)	605,895
Status	Completed
Type	Research Grant
Start date	14/10/2013
End date	13/04/2018
Duration	54 months

Abstract

Functional genomics is the study of how the organism works, in the context of the genes encoded by its genome. A key question when understanding what a gene does is to see when and where it is expressed. Then we can mutate the genes in a simple model organism, and see what changes in those tissues - this is called 'reverse genetics', and is a key part of post-genomic research. The simple fruit fly Drosophila is an excellent model for such studies, because of its uniquely powerful genetic resources and reverse genetic tools, and is used by many thousands of labs around the world. As well as being an important organism to study in its own right, it has proved a valuable model both for human function and disease, and for study of closely related insect pests and vectors of disease. In 2007, we produced FlyAtlas.org, an online atlas of gene expression across multiple tissues (brain, heart, gut, muscle etc) of both larval and adult flies, using the then cutting-edge technology of Affymetrix microarrays. This database revealed a great hunger for such data, both in the Drosophila research community and beyond, and the data have already been used in over 650 papers. However, we now plan to extend these data with RNA-seq and small RNA-seq, with samples painstakingly dissected from at least 30 distinct tissues., in multiple replicates, to provide a much more complete picture for the community. In particular, we are not constrained by the genes printed on the Affymetrix chips, and can identify and measure the abundance of different transcripts from any gene. In addition, we will be able to identify novel variants of known transcripts, or even entirely new genes. We will also be able to map out the expression of small RNAs, notably miRNAs across multiple tissues. The result will be a step-change in how we are able to perform post-genomic research, both in Drosophila, and in economically important related insect species.

Summary

Now that many genomes (of humans and other organisms) have been sequenced, we know that most animals are made with about 15 000 - 25 000 genes. Perhaps surprisingly, we still do not know what all these genes do, and we are still discovering entirely new genes. A vital tool to understanding what genes do is simply to see where the genes are being used (or "expressed"). Then we can mutate the genes in a simple model organism, and see what changes in those tissues - this is called 'reverse genetics', and is a key part of post-genomic research. The simple fruit fly Drosophila is an excellent model for such studies, because of its uniquely powerful genetics, and is used by many thousands of labs around the world. As well as being an important organism to study in its own right, it has proved a valuable model both for human function and disease, and for study of closely related insect pests and vectors of disease. In 2007, we produced FlyAtlas.org, an online atlas of gene expression across multiple tissues (brain, heart, gut, muscle etc) of both larval and adult flies, using the then cutting-edge technology of Affymetrix microarrays. With this resource, users could quickly (in typically 10 seconds) get an answer to the question "where and when in the organism is my gene of interest expressed?" As FlyAtlas saves the need to go off and do a series of expensive experiments, this website thus saves many days of work each time it is used. This database revealed a great hunger for such data, both in the Drosophila research community and beyond, and the data have already been used in over 650 papers from around the world. However, since then the technology has rapidly advanced, and 'next generation sequencing (NGS)' allows us to provide a much more complete picture. In particular, we are not constrained by the genes printed on the Affymetrix chips, and can identify and measure the abundance of different transcripts from any gene. In addition, we will be able to identify novelvariants of known transcripts, or even entirely new genes. We will also be able to map out the expression of tiny, 'micro RNAs' across multiple tissues. The result will be a step-change in how we are able to perform post-genomic research. All these data will be placed rapidly online -in the public domain- to inform and accelerate research worldwide. We will also work to evanglise the new, extended FlyAtlas resource both to the Drosophila community and beyond. As well as obvious benefits to scientists, the data will enable biomedical research using Drosophila, as many researchers are now successfully modelling human diseases in flies. Additionally, the work will benefit industry, as the data will help to inform the search for new classes of safer, 'greener' insecticides. This is important, because insects are major vectors of disease, and pests of crops, around the world.

Impact Summary

The key deliverables of this project are a unique dataset, and a readily- understood user interface to aid take-up by a broad constituency. The key beneficiaries are: Academe: Drosophila biologists, insect biologists, biomedical scientists, informaticians, systems biologists A key advantage to our efforts is that FlyAtlas 1.0 already has a very high take-up in the target constituencies, and is regularly accessed (tens of thousands of times per year) and its existence mentioned in dozens of papers every year. Therefore, users will be pulled naturally towards the new datasets as they arrive online. To best engage them, we therefore need to continue to update our website, maintain our domain registration, and circulate the community regularly with news of updates (which we do by posting to multiple bionet usenet groups). Further outreach (aimed at further improving take-up in our target constituencies) is outlined in the proposal. Briefly, we will present at, or run workshops in, key world conferences (the international Drosophila meeting, and Insect molecular science meeting). We already do this for FlyAtlas 1.0. Industry: Agrochemical industry, Pharmaceutical industry, biomedical companies For take-up by industry, we will build on our collaborative links. Our group is in close contact, or active collaboration, with major and emerging players in the agrochemical industry (for example, Pfizer Veterinary Medicine Discovery Research, BASF, Bayer, Syngenta and Unilever), and we know these companies already use FlyAtlas extensively. So roll-out of new data will not be an issue. For broader outreach to the food security and biomedicine communities, we have recently written articles in major public-sector publications with wide circulations in academia, industry, research organizations and politics. (Public Service Review: UK Science and Technology v. 7; International Innovation, September 2012). Broad Education Landscape: Life science, computing and bioinformatics students (school, undergraduates and postgraduates) There is already broad take-up of FlyAtlas at the Undergraduate and Postgraduate level, associated with life science and computing projects. To improve the accessibility of our data to this level, we propose to add tutorial pages to our website, and to maintain clarity and simplicity of design on the web-pages. We have been quite impressed at the ability of final-year Undergraduate Honours students to take to quite advanced data mining projects using FlyAtlas as a resource. We also have outreach projects to biology students in schools. We have hosted local work experience and summer students in our labs. Every year, we engage in an extended collaboration with one of the best sixth form colleges in Singapore, Hwa Chong Institution, and host a group of 6 students for a week to give them lab experience, and to design projects they can perform back in Singapore. We then mentor progress in these projects over an extended period.

Committee	Closed Committee - Animal Sciences (AS)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	Bioinformatics and Biological Resources Fund (BBR) [2007-2015]
Funding Scheme	X – not Funded via a specific Funding Scheme

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