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

Lead Research Organisation: University of Glasgow
Department Name: College of Medical, Veterinary &Life Sci

Abstract

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 novel variants 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.

Technical Summary

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.

Planned Impact

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.
 
Description We have updated the widely used flyatlas.org resource with new data based on next generation sequencing. As well as an atlas of tissue-specific gene expression, we have expanded the resource with separate data for male and female flies, data of great value for the field. We have also produced the first comprehensive micro RNA data for multiple tissues in Drosophila.
Exploitation Route The original flyatlas dataset has now been mentioned in over 1700 papers. These updated data will immediately inform all Drosophila research worldwide, and also those using (or thinking of using) Drosophila as model system for biomedical research.
Sectors Agriculture, Food and Drink,Digital/Communication/Information Technologies (including Software),Environment,Pharmaceuticals and Medical Biotechnology

URL http://flyatlas2.org
 
Description NIH Centre grant
Amount $400,000 (USD)
Funding ID DK100227 
Organisation National Institutes of Health (NIH) 
Sector Public
Country United States
Start 03/2013 
End 03/2018
 
Title RNAseq midgut database 
Description RNAseq profiles for different pH regions of midgut. COpublished with a MS. 
Type Of Material Database/Collection of data 
Year Produced 2016 
Provided To Others? Yes  
Impact none yet. 
URL http://www.ebi.ac.uk/ena/data/view/PRJEB11865
 
Description Collaboration with BASF 
Organisation BASF
Country Germany 
Sector Private 
PI Contribution Based on our leading position in insect biology and functional genomics, we have had longstanding collaborations with BASF in RTP, North Carolina. We have performed extensive contract research over 5 years, and continued to discuss possibilities for the development of new targets. We have also tested novel compounds from BASF against in-house assays.
Collaborator Contribution BASF have funded extensive periods of contract research with our group, and paid us for consultancy when testing novel compounds. They have also hosted a FLIP award with our group, led by Professor SHireen Davies, giving us access to leaders in several of the key chemistry, mode-of-action and regulatory groups in North Carolina. This has informed our plans to develop a spin-out from our research.
Impact Large gene expression datasets and fly lines developed. Details are confidential.
 
Description Collaboration with Bayer 
Organisation Bayer
Department Bayer CropScience Ltd
Country United Kingdom 
Sector Private 
PI Contribution Our identification of processes involved in the generation of extreme pH in insect guts has the potential to lead to new, greener, more selective insecticides at a time when there is field resistance to all commercial insecticides. This work has led to approaches from industry.
Collaborator Contribution Bayer approached us to discuss our plans to commercialize this research. They duly completed 2-way NDAs with the University of Glasgow, and held a conference call with us in February 2018. They are excited by the possibilities, and plan to discuss further once the merger with BASF is complete.
Impact N/A
Start Year 2017
 
Description Glasgow Science Week 2016 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact A stand at Glasgow University's open day for the Glasgow Science Festival. Supported by multiple members of our group.
Year(s) Of Engagement Activity 2016