The Digital Fruit Fly Brain

Lead Research Organisation: University of Sheffield
Department Name: Automatic Control and Systems Eng

Abstract

Several highly ambitious, large-scale, billion-pound research projects that aim to understand the human brain are currently under way. In Europe, The Human Brain Project is focused on accelerating brain research by integrating data available from a multitude of disparate research projects through the development of a multi-scale, multi-level model of the human brain - the 100 billion neurons modelling and simulation challenge. In US, The Brain Initiative aims to reconstruct the full record of neural activity across complete neural circuits - the 100 billion neurons recording challenge. These are clearly huge but worthy challenges that, we believe, can benefit from an understanding of the principles of neural computation of much smaller but sufficiently complex brains.
The fruit fly brain has become one of the most popular model organisms to study neural computation and for relating brain structure to function. Many of the genes and proteins expressed in the mammalian brain are also conserved in the genome of Drosophila. Remarkably, the fruit fly is capable of a host of complex nonreactive behaviors that are governed by a brain containing only ~100000 neurons. The relationship between the fly's brain and its behaviors can be experimentally probed using a powerful toolkit of genetic techniques for manipulation of the fly's neural circuitry. Novel experimental methods for precise recordings of the fly's neuronal responses to stimuli and for mapping neurons and synapses in Drosophila nervous system have provided access to an immense amount of valuable data regarding the fly's neural connectivity map and its processing of sensory stimuli. These features coupled with the growing ethical and economic pressures to reduce the use of mammals in research, explain the growing interest in Drosophila-based brain models, not only to understand sensing, perception and neural computation but also to elucidate human neurodegenerative diseases such as Alzheimer's disease.
Despite significant investment and huge progress in understanding Drosophila neural circuits and the availability of excellent genomic and genetic community databases, a major obstacle in understanding the fly brain is the lack of communication/collaboration across the modelling community as well as lack of shared models, modelling tools and data repositories. Vast amounts of experimental data that have yet to be distilled into new models or used to validate and refine existing models, have been generated by labs around the world. Knowledge and information of the detailed neuroanatomy, neuron connectivity and gene expression of the adult Drosophila melanogaster brain has been made publicly available thanks to the efforts of earlier pioneering efforts.
This aim to develop an open source, modular software platform that will help researchers to work collaboratively and exploit the wealth of knowledge, data, models, and tools available to build and simulate a complete model of the fly brain. The software platform exploits relatively cheap supercomputing services that use Graphic Processor Units, which many academic institutions in the UK, US and worldwide haave adopted in recent years.

Technical Summary

This project aims to design, implement and experimentally evaluate a potentially transformative open-source fly brain simulation platform capable of simulating ~135,000 neurons that make up the adult Drosophila brain. This computational infrastructure will be based on the recently established GPU-enabled Neurokernel software platform. The modular simulation platform will integrate all knowledge about the Drosophila brain as a set of interconnected simulation modules which describe the operation of about 41 Local Processing Units (LPUs), six hubs and their interconnections, partly elucidated by detailed EM imaging studies. The simulation platform will be used to develop and validate a first draft model that incorporates the most advanced biophysical and/or functional models of the neurons and the latest published synaptic connections maps. The main focus will be on developing detailed models of the early visual system (retina, lamina, medulla) and of the early olfactory system (OSNs, antennal lobe, mushroom body, lateral horn). These models will integrate complete models of the visual and olfactory systems. The brain simulation platform will enable for the first time the isolated and integrated emulation of fly brain model neural circuits and their connectivity patterns (e.g., sensory and locomotion systems) and other parts of the fly's nervous system on clusters of GPUs. Using the Neurokernel simulation platform it will be possible to generate data sufficiently fast to enable researchers to compare and tune the input-output characteristics of virtual neurons on-line, while the experiment is running.

Planned Impact

The end-users of this research are anticipated to be:
a) NVIDIA (Project Partner)
As many universities have invested in GPU-based commodity supercomputing services, NVIDIA is very interested to understand and meet the needs of the science community in order to develop successful products for very competitive market. It should be noted that big players like Intel and IMB are in direct competition with NVIDIA in the High-Performance Computing/Supercomputing market. As Project Partner NVIDIA will have direct, first-hand access to our results. The project will give the valuable insight into the current limitations of, particularly, their connectivity architecture for such applications. NVIDIA will also have access to novel software architectures that exploit parallelism, which will enable them to optimize and develop further their CUDA tools, libraries, languages and other development tools.
b) Rolls-Royce
The Automatic Control and Systems Engineering Department at the University of Sheffield hosts the Rolls-Royce University Technology Centre in Control and Systems Engineering (RR-UTC). RR-UTC provides the company with the necessary technology to support the efficient production of world-class engine control and monitoring systems. The Centre recently achieved economic impact by developing the first radically new control laws for gas turbine engines for 30 years, which are now operating across the entire engine range, including the flagship Rolls-Royce Trent 1000 engines powering the Boeing Dreamliner.
One of the research areas being investigated within the Centre is the use of compressive sensing techniques for efficient, transmission and reconstruction of the signals from the sensors acquiring the data. This has the potential to reduce significantly the bandwidth required for data transfer from a vast array of sensors and pave the way for the implementation of wireless control systems. Another area of active research is in distributed decision support systems for health management of the fleet of engines, supported by high performance computing architectures. The proposed project is of particular interest because the brain employs exactly the type of low-energy, low bandwidth but highly robust coding strategies that are desired by the company. Moreover, by understanding the brain, which in effect is a highly sophisticated control system, it would be possible to develop alternative neuromorphic distributed control architectures which could be much cheaper to implement as well as more robust and fault tolerant.

Publications


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Friederich U (2016) Fly Photoreceptors Encode Phase Congruency. in PloS one
 
Description We demonstrated that fly photoreceptors use nonlinear transformations of visual stimuli to encode efficiently edges present in temporal stimuli.
Specifically we showed recently that nonlinear encoding achieves near optimal rate/distortion bound.

We have demonstrated that photoreceptors use a nonlinear coding scheme to improve communication robustness in noisy environments
Exploitation Route Improve the design of artificial retinas
Development of new bio-inspired, robust information processing and coding strategies
Sectors Aerospace, Defence and Marine,Healthcare
URL http://www.dflybrain.org
 
Description The Fruit Fly Brain Observatory we developed is a great education resource that has started to be used by educators. It provides a Natural Language Interface allowing nonexperts to query and explore the fruit fly brain using normal language.
First Year Of Impact 2016
Sector Education
Impact Types Societal
 
Description Fruit Fly Brain Observatory-Open Science Prize Competition
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
Impact Mental and neurological disorders pose major medical and socioeconomic challenges for society. Understanding human brain function and disease is arguably the biggest challenge in neuroscience. To help address this challenge, smaller but sufficiently complex brains can be used. This application will store and process connected data related to the neural circuits of the fruit fly brain. Using computational disease models, researchers can make targeted modifications that are difficult to perform in vivo with current genetic techniques. These capabilities will significantly accelerate the development of powerful new ways to predict the effects of pharmaceuticals upon neural circuit functions. Using computational disease models, researchers can make targeted modifications that are difficult to perform in vivo with current genetic techniques. Models of neural circuits affected by disease will enable parallel recording of the responses of multiple components of a model circuit that are currently difficult - if not impossible - to perform in vivo. These capabilities will significantly accelerate the development of powerful new ways to predict the effects of pharmaceuticals upon neural circuit functions.
URL https://www.nih.gov/news-events/news-releases/open-science-prize-announces-six-team-finalists-first-...
 
Description Microsoft Azure for Research
Amount $5,000 (USD)
Funding ID CRM:0518115 
Organisation Microsoft Corporation 
Sector Public
Country United States of America
Start 01/2017 
End 12/2018
 
Description Open Science Prize
Amount $80,000 (USD)
Organisation The Wellcome Trust Ltd 
Sector Charity/Non Profit
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 04/2016 
End 12/2016
 
Title Fruit Fly Brain Observatory 
Description Mental and neurological disorders pose major medical and socioeconomic challenges for society. Understanding human brain function and disease is arguably the biggest challenge in neuroscience. To address this challenge, smaller but sufficiently complex brains like that of the fruit fly have been increasingly used for investigating the mechanisms of human neurological and psychiatric disorders, such as Epilepsy or Parkinson's disease, at molecular, cellular and circuit level. The Fruit Fly Brain Observatory (FFBO) is an open source software platform that stores and processes data related to the neural circuits of the fly brain including location, morphology, connectivity and biophysical properties of every neuron; seamlessly integrates the structural and genetic data from multiple sources that can be queried, visualized and interpreted; automatically generates models of the fly brain that can be simulated efficiently using multiple Graphics Processing Units (GPUs) to help elucidate the mechanisms of human neurological disorders and identify drug targets. 
Type Of Material Improvements to research infrastructure 
Year Produced 2016 
Provided To Others? Yes  
Impact Using computational disease models, researchers make targeted modifications that are difficult to perform in vivo with current genetic techniques. Models of neural circuits affected by disease will enable parallel recording of the responses of multiple components of a model circuit that are currently difficult - if not impossible - to perform in vivo. These capabilities significantly accelerate the development of powerful new ways to predict the effects of pharmaceuticals upon neural circuit functions. The software platform has been used to develop and simulate models of Parkinson's disease, retinal degeneration and epilepsy. 
URL http://fruitflybrain.org/
 
Title NeuroGFX and NeuroNLP 
Description NeuroNLP provides a modern web-based portal for navigating fruit fly brain circuit data. It enables in-depth exploration and investigation of brain structure, using intuitive plain English queries, such as "show glutamatergic local neurons in the left antennal lobe". NeuroNLP can be accessed from any browser supporting WebGL. NeuroGFX is a database and user interface for executable neural circuits. With an intuitive graphical interface that visualizes biological circuit and their corresonding circuit diagrams with a hierarchical structure, NeuroGFX makes it easy to reconfigure brain circuits stored in the database, and, most importantly, execute them on GPUs to explore functions of the intact and reconfigured circuits. It presents a brain architecture in which models of different parts of the fruit fly brain can be integrated towards the exploration of whole brain function. 
Type Of Material Database/Collection of data 
Year Produced 2016 
Provided To Others? Yes  
Impact The system has been used to implement and simulate models of neurodegenerative disease. It is currently being used by a number of research labs. It cal also be used as an educational tool. 
URL https://neuronlp.fruitflybrain.org/
 
Description Bionet 
Organisation Columbia University
Department Electrical Engineering
Country United States of America 
Sector Academic/University 
PI Contribution We developed, and refined models of the retina for simulation on the Neurokernel platform.
Collaborator Contribution Developed the initial open source simulation platform Neurokernel. Provided tools and resources for our group to use.
Impact Open Science Prize Application This is a multi-disciplinary collaboration to develop models and a software platform for simulating the entire brain of the fruit fly: biology, computer science, control and systems engineering
Start Year 2015
 
Description NVIDIA 
Organisation NVIDIA
Country Global 
Sector Private 
PI Contribution Evaluation of new GPU architectures
Collaborator Contribution Training and technical support. In-kind contribution of £30K
Impact None yet
Start Year 2015
 
Description Oxford 
Organisation University of Oxford
Department Department of Physiology, Anatomy and Genetics
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution We are developing modelling and simulation tools to make experimentally plausible and accurate models of the fruit fly brain.
Collaborator Contribution They support the drosophila brain project with data, evaluation & testing of the software, and to help validate models.
Impact No outputs yet. Multi-disciplinary: biology, systems engineering, control engineering
Start Year 2015
 
Description Cosyne 2017 Computational Neuroscience Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact We had the opportunity to demonstrate the Fruit Fly Brain Observatory prototype- our entry for the final of the Open Science Prize
(http://fruitflybrain.org/)
Year(s) Of Engagement Activity 2017
 
Description Fly Brain Hackathon 2016 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Workshop organised at Columbia University in New York aimed at providing training and introducing participants to the modelling, simulation and visualisation tools developed as part of this project.
Year(s) Of Engagement Activity 2016
URL http://www.bionet.ee.columbia.edu/hackathons/ffbh/2016
 
Description Fruit Fly Brain Hackathon 2017 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact The 2nd Fruit Fly Brain Hackathon (FFBO 2017) and the first to feature the Fruit Fly Brain Observatory (FFBO) and its key components NeuroNLP and NeuroGFX. The former allows for exploring fruit fly brain data using plain English queries, and the latter facilitates the modeling and execution of such brain circuits. Brief tutorials will be given on the usage of the FFBO as well as developing new tools/features in FFBO. The hackathon is aimed at three main groups of participants: neurobiologists, modelers and software engineers. The goal of the hackathon is to bring together these three groups of participants to develop, use and improve the FFBO platform towards developing executable models of the fruit fly brain.
Year(s) Of Engagement Activity 2017
URL http://www.bionet.ee.columbia.edu/hackathons/ffbh/2017
 
Description Open Data Science Symposium: How Open Data and Open Science are Transforming Biomedical Research 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Funding agencies and biomedical research organizations are increasingly embracing Open Science research paradigms characterized by new models of collaboration, new modes of data sharing, and new requirements for making data publicly available. The growing availability of open biomedical data and cloud-based infrastructure is creating unprecedented opportunities for using biomedical Big Data in novel ways to help solve pressing public health and biomedical research challenges.

This Symposium featured the Six Team Finalists of the Open Science Prize, an international prize competition led by the NIH Big Data to Knowledge (BD2K) Initiative, in partnership with the Howard Hughes Medical Institute and the UK-based Wellcome Trust, to support the development of innovative tools, products, and services that utilize Open Data.

Our Fruit Fly Brain Observatory prototype was one of the Six Team Finalists (https://www.openscienceprize.org/res/p/finalists/).
At this event, the six projects were made available the Open Science Prize website for the general public to vote.

Public voting comments comments on our Fruit Fly Brain Observatory are summarized below:
• Brain is the final frontier for sure. I really appreciate the effort the neuroscientists put into for better understanding brain and its function, especially for a moderate but achievable aim.

• Such a fantastic competition. I certainly see that linking connectome data with functional imaging data will be the next great revolution in science, and the difficulty and significance will dwarf the findings from the genome project and its relation to gene function. While this is my opinion, I certainly believe that understanding brain function will be massively more difficult than gene function, particularly as gene function can be done one at time but brain function needs to understand multiple interconnecting circuits simultaneously just to understand one small part of the brain. This I would definitely promote the fruit fly brain observatory.

• First, I think the brain researches help we human beings understand what we are, and what we can do next. Even a fruit fly's brain will tell lots of we never know before. Thus, I vote Fruit Fly as the 1st prize.

• I am more fascinated with all teams. they have done wonderful job. we know invertebrate system has given us excellent opportunity to understand the brain. FFBO has given a really good step by open source platform which includes brain imaging techniques, connectivity, morphology and tracing pattern of neurons spanning throughout in brain which will permit us to comprehend the human brain function and its disease related functions that is the biggest challenge in neuroscience.

• I am really convinced that the proper modelling could save time and resources in research. I liked the fact that the fruit fly observatory project could open other doors into the modelling and analysis of multiple diseases which in turn could lead to a quicker solution.

• I believe that Fruit Fly Brain Observatory concept is were the future of the discovery in medicine - creating interactive prototypes/models that would help identifying roots of the problems and finding resolutions by experimenting with the model. Similarly, new drug discovered via candidates compounds modeling.

• I like that the fruit fly brain observatory has very advanced technology that can allow researchers to perform genetic experiements using software.

• I like the idea of mapping the brain like an electrical system. I had some trouble with the website functionality, and as an IT professional, that needs refined. I also participate in Alzheimer's research as a subject, and see value in anything that can help us defeat this awful disease and many brain diseases that have eluded us so far.

• I vote for the Fruit Fly Brain Observatory since I think that this project has the potential to lead to ground breaking research and could have high impact. The project considers engineering aspects (such as modelling, simulation aspects and computational power) and medical aspects as well.

• If one is to "reverse engineer" the workings of the brain, it makes a lot of sense to start with a simple organism (fruit fly) where one can study small scale neuron interactions. Furthermore, the fruit fly has been very widely studied and consolidating what is known will be very useful. I tried out the system and found it easy to use with very nice visuals.

• Its really beautiful project and research.

• Kudos to all who worked on these prototypes. I wish they could all win. I chose the ones that I hope will advance the efforts to prevent or cure Alzheimer's and other dementias.

• Neurodegenerative diseases are more prevalent worldwide as the human population accumulates aged persons. The Drosophila model is excellent depiction of how we can address the neurodegenerative process in diseases like Alzheimer's and Parkinson's. Drosophila is an excellent model to understand the mechanism(s) of human disease pathologies. This team deserves the first prize.

• Thanks for these great works on SciVis. I am glad to see people to use the power of visualization to improve human life.

• Selected project will help cure mental disorder.

• The data and tools of the Fruit Fly Brain Observatory are pretty awesome, extensive and forward looking! I believe it'll be a pathblazing tool for other organisms as well as they scale up in the years to come.

• The fruit fly brain observatory is a very effective integration of known data and will be very useful to the international neuroscience community.

• The Fruit Fly Brain Observatory is important because we don't want films like Contagion to happen in real life. We need to study brains.

• The fruit fly brain observatory seems promising given that this research could unlock several mysteries to understand the human mind and fight serious degenerative diseases like Parkinson and Alzheimer.

• The Fruit Fly Brain project, seems to have the potential to revolutionize research in blindness.

• The human brain is the beginning and end of every human problem. To understand the brain is to understand avenues to both problems and solutions.

• The most useful for my research!

• Understanding how a brain works is one of the great challenge for this century. Given the complexity of the problem at hand, integrative and large scale approaches are needed to map the architecture. Fruit Fly Brain Observatory is an elegant platform attempting to address these immense challenges. By integrating massive amounts of neuroanatomy data in a common space, and making it approachable to other scientists will go a long way in contributing to the understanding of brain.

• As recession hits the major markets, the funding for an important part of research (basic research) get cut down. I believe this type of modelling should continue no matter what the state of world's capital markets as this type of research is responsible for increasing the real knowledge of the mankind.

• I am most interested in the Open Brain Imaging because I am battling brain cancer. I would love to see this projecs help advance neuroscience to help patients like me in the future.

• There is value in all of the studies. I voted for the two that studied the brain. The brain is our key to life. It holds the secrets of mental illness, including depression, which is one of the largest causes of disability worldwide. Through learning more about the brain we will be able to provide more effective treatments, and hopefully find ways to prevent the development of mental and neurological illnesses.
Year(s) Of Engagement Activity 2016
URL https://datascience.nih.gov/OpenDataScienceSymposiumCal