Award details

Reverse-engineering Drosophila's retinal networks

Reference	BB/H013849/1
Principal Investigator / Supervisor	Professor Daniel Coca
Co-Investigators / Co-Supervisors	Professor Stephen Billings, Professor Mikko Ilmari Juusola
Institution	University of Sheffield
Department	Automatic Control and Systems Eng
Funding type	Research
Value (£)	532,115
Status	Completed
Type	Research Grant
Start date	16/08/2010
End date	15/02/2014
Duration	42 months

Abstract

This project aims to identify and characterize quantitatively, within a control and systems engineering framework, the regulatory mechanisms that underpin the robust operation of retinal circuits, the 'tuning' strategies by which these adapt to changes in their visual environment and the information theoretic goals that govern network adaptation. In order to accomplish these aims, we will develop a detailed biophysical model of the R-LMC-R visual processing module in Drosophila, using a data-driven reverse-engineering approach that we pioneered, which combines nonlinear system identification and frequency response techniques with conventional reductionist methods rooted in molecular biology.

Summary

Vision is the most important sense of many living organisms. Even in the dimmest habitats animals have functional eyes, which allow them to extract useful optical information from the environment and to respond rapidly and appropriately to changing events and conditions. The anatomical structure, molecular signalling cascades and ultimately the performance of an organism's visual system, measured in terms of speed, sensitivity, dynamic range and robustness, has been tuned to suit its lifestyle by the content of the photic stimuli as well as other environmental factors. Vision of invertebrate species was the subject of extensive research which led to the discovery of important fundamental principles that apply to all senses. Drosophila visual system is an ideal model to investigate the mechanisms underlying early neural processing with a wealth of detailed knowledge from tens of years of genetic, anatomical, physiological and behavioural studies. The ultrastructure of the first visual synaptic layer in Drosophila has been fully described from electron-micrograph sections. A vast array of molecular genetic methods combined with biochemical analysis and intracellular recording techniques have converged on Drosophila's visual system providing unprecedented experimental tractability. These methodologies have made possible the identification of elements of its signalling cascades and offered unique insight into the associated regulatory mechanisms. The signal-processing capability of fly photoreceptors is prodigious, outperforming human engineered image sensors in many respects. They are exquisitely sensitive, being able to respond to single photon events. Weak input signals embedded in noise can be selectively amplified and filtered to provide efficient and reliable sensing of physiologically relevant stimuli. A fascinating functional attribute of photoreceptors, that is yet to be replicated in an engineering sensing device, is their ability to light adapt, i.e. adjust the amplification gain, according to both past and on-going light events, using many layers of positive- and negative-feedback control. This allows them to operate over a wide environmental range. They can reliably respond to the absorption of single photons under dark-adapted conditions, but can also adjust the gain to operate in bright daylight conditions. This project aims to develop, using mathematical tools and techniques borrowed from control and systems engineering, a detailed mathematical model the early vision system that will allow us to understand the role of different molecular components that are instrumental in converting light into electrical signals and the adaptation rules that fly photoreceptors must obey in order to operate reliably in dark as well as in full shinshine.

Impact Summary

Beneficiaries The immediate beneficiary of knowledge arising from this research is anticipated to be its end-users in the wide scientific community, from biological sciences to engineering to applied mathematics. They will profit from increased understanding of the visual system of invertebrates. More specifically, the following groups have been identified as potential beneficiaries: Group A. Scientists researching sense systems, particularly vision Group B. Scientists, practitioners, companies involved in drug discovery/synthetic Biology Group C: Mathematical modellers, computational biologists Group D: Academics and engineers involved in the development of artificial eyes Communications and Engagement 1.Publications in peer-review journals and conferences (Groups A,B,C,D) 2.Development of a website detailing both the ultrastructure of te laminar cartridge and a on-line simulation model of the adaptive retinal network. (Groups A,B,D) 3.Development of a modular simulation model in matlab of Drosophila's phototransduction cascade that can be shared with other research groups and can be easily upgradable by other researchers.(Groups A,B,C) 4.Make contacts with research groups and companies involved in drug discovery and synthetic biology. (Groups B) 5.Make contacts with research groups, companies involved in robotic vision (Group D) 6.Disseminate results at workshops organized by the Sheffield Synthetic Biology Network (Group B)

Committee	Research Committee C (Genes, development and STEM approaches to biology)
Research Topics	Neuroscience and Behaviour, Systems Biology
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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