Richard Benton, Professor

Our current work comprises three, interrelated research themes. More information can be found in our publications, our pre-prints or by contacting us.

Structure and function of sensory Ionotropic Receptors

Since our discovery in 2009 of Ionotropic Receptors (IRs) – a subclade of the ionotropic glutamate receptor superfamily of ligand-gated ion channels – as a novel family of insect olfactory receptors, we and others have shown that these proteins have evolved diverse roles in olfaction, gustation, hygrosensation and thermosensation across insects. IRs form heteromeric complexes of “tuning” receptors, which define stimulus specificity, and one or more co-receptor subunits, which function in subcellular trafficking and signalling. We are currently developing in vivo, in vitro and in silico approaches to understand the mechanisms and evolution of ligand-recognition, heteromeric complex assembly and channel gating.

Evolutionary neurodevelopmental biology of olfactory circuits

Olfactory pathways are one of the most dynamically evolving parts of the nervous system: animals frequently acquire (and discard) olfactory receptors, circuits and odour-evoked behaviours with the ever-changing landscape of stimuli in their environment. The evolutionary flexibility of olfactory systems is reflected in their modular organisation: in insects (as in vertebrates), most individual olfactory sensory neurons (OSNs) express just one olfactory receptor gene, and the axons of OSNs expressing the same receptor converge on discrete regions of neuropil (glomeruli) within the primary olfactory centre, where they synapse with second-order neurons. The numbers of olfactory receptors vary widely across species, with concordant diversity in the number and organisation of OSNs and glomeruli in the brain.

Using molecular genetic, single-cell sequencing and circuit tracing approaches in the D. melanogaster peripheral olfactory system, we are studying the mechanisms and evolution of (i) neuronal lineage specification, (ii) olfactory receptors’ singular expression patterns, (iii) how novel populations of OSNs arise through changes in patterns of neurogenesis and developmental programmed cell death, and (iv) how OSN populations are segregated to distinct glomeruli to form unique sensory channels in the brain. The mechanisms and molecules we characterise are likely to be relevant for understanding circuit formation and evolution in other brain regions and species.

Drosophila sechellia: a novel neurogenetic model

How animals’ extraordinarily diverse behaviours have evolved is unknown. Relating interspecific behavioural differences to anatomical or physiological distinctions in neural circuits, and causal genetic variation, offers a powerful approach to inform how nervous systems develop, function and change. We are establishing a new model neurogenetic system, Drosophila sechellia, an island endemic that is closely related to D. melanogaster and D. simulans. While D. sechellia retains global genomic and superficial morphological similarity to its cosmopolitan generalist cousins, this species has adapted to a unique ecological niche, using Morinda fruit as a sole host for feeding and breeding. This work, which now takes our lab beyond the olfactory system, is being developed through three main aims:

(i) Establishment of a D. sechellia (neuro)genetic toolkit: we are building essential genetic reagents for generation and maintenance of animals of desired genotypes, for neurogenetic manipulations, and for recombination mapping-based approaches.

(ii) Behavioural, neuroanatomical and molecular phenomics: systematic comparison of D. sechellia, D. simulans and D. melanogaster for their behaviours, their neuroanatomy and their neuro-molecular expression properties should reveal how D. sechellia has adapted to its niche, and will provide multiple entry-points to relate molecular, neuronal and behavioural differences between these species.

(iii) Defining the genetic basis and functional significance of neuronal adaptations in D. sechellia: through high-resolution quantitative trait mapping and interspecific allele swap approaches, we aim to identify the causal genetic changes underlying neural adaptations in D. sechellia, and their physiological and behavioural significance.

Alumni: where are they now?

	Iris Marouani - Administrative Assistant
	Liliane Abuin - Technician Liliane obtained her Diplôme de Technicienne en Analyses Biomédicales from the Ecole Cantonale Vaudoise de Laborantins et Laborantines Médicaux. During 1996-2007 she worked in the group of Susanna Cotecchia in the Department of Pharmacology and Toxicology at the University of Lausanne. She has worked in the lab since October 2007.
	Raquel Alvarez Ocana - PhD Student Raquel Alvarez Ocaña obtained her Bachelors in Biology from the Autonomous University of Madrid in 2015. During her degree, she worked in Isabel Correas’s laboratory on biochemical and functional characterization of 4.1/Coracle protein in Drosophila, and in Ana Busturia’s laboratory investigating MDM2 expression and p53-dependent apoptotic factors in Drosophila melanogaster cells. In September 2015 she started her Masters in Medical Biology at UNIL, working in Angela Ciuffi’s group for her First Steps Project on the resurrection of a zebrafish endogenous retrovirus. She joined our group in February 2016, first as a Master student, and before staying on for her PhD, to perform a comparative analysis of olfactory pathways in drosophilids.
	Jonas Barraud - Apprentice Technician Jonas is from St-Saphorin and joined our lab in Jan 2020 as part of his technician apprenticeship.
	Alberto Maria Cattaneo - Visiting Post-doctoral Fellow Alberto Maria obtained his Bachelor and Master degrees in Plant Biotechnologies at the University of Milan, Italy, where he was working on protein targeting in plant cells in collaboration with other European Universities: Warwick, UK (2008) and BOKU, Austria (2010). He received his PhD in molecular biology on 2015 at Fondazione Edmund Mach, Italy, working in collaboration with the Whitney Lab of the University of Florida, where he functionally characterised ORs and TRP-channels of insects and mammals by their heterologous expression in HEK cells. After a post-doctoral fellowship at the University of Cagliari, Italy, in 2017, Alberto Maria pursued a post doc in the division of Chemical Ecology of SLU-Alnarp, Sweden, doing the functional characterisation of insect ORs by GC-SSR. Currently, Alberto Maria is visiting our lab with a FORMAS mobility grant from Sweden to functionally characterise ionotropic receptors (IRs) of pest insects by the use of heterologous cell systems.
	Steeve Cruchet - Technician Steeve obtained his Diploma of Technician in Biomedical Analysis from the Ecole Cantonale Vaudoise de Laborantins et Laborantines Médicaux. From 2007 to 2010 he worked in the group of Thierry Pedrazzini in the Unity of Experimental Cardiology at the University Hospital of Lausanne. He joined the lab in March 2011.
	Daehan Lee - Post-doctoral Fellow Daehan obtained his PhD from Seoul National University where, in Junho Lee’s lab, he sought the genetic basis and natural variation of Caenorhabditis elegans "hitchhiking" behaviour. Following his PhD, he carried out post-doctoral research with Erik Andersen's group at Northwestern University, USA. There, he investigated natural genetic variation across wild C. elegans strains and studied how natural selection shapes the genomes and phenotypes of this species. He joined our group in July 2020, and will dissect the genetic and molecular basis of nervous system evolution in drosophilids through cross-species quantitative neurogenetics.
	Jérôme Mermet - Post-doctoral Fellow Jérôme obtained his Bachelor and Master degrees from University of Toulouse in France where he studied epigenetic regulation of gene expression in breast cancer cells in the lab of Kerstin Bystricky. He then joined the lab of Félix Naef at the EPFL, Switzerland, to study the dynamics of the three-dimensional organisation of chromatin across the circadian cycle and its function for circadian-clock gene transcription in mouse tissues. He joined our lab in April 2019 to investigate molecular mechanisms modulating olfactory circuit architecture during development in Drosophila.
	Kaan Mika - PhD Student Kaan obtained his Bachelors in Molecular Biology and Genetics from Istanbul Technical University in 2012, where he studied the effect of Nuclear Factor 1 family transcription factors on hind brain development under the supervision of Aslı Kumbasar. During his degree, he studied two semesters at Roskilde University where he worked on two independent projects under the supervision of Kim Furbo Rewitz and Birgit Koch, respectively. He then obtained his Masters in Molecular Biology and Genetics from Boğaziçi University in 2014 working in the laboratory of Arzu Çelik, where he focused on the development of the Drosophila olfactory system. He joined our lab as a visiting student in Jan 2015, working with Lucia Prieto, before beginning his PhD in the group in Dec 2015. Check out his other scientific interests on Slice of Science!
	Hayden Schmidt - Post-doctoral Fellow Hayden received his Bachelor’s degree from Whittier College in 2014, where he worked with Dr. Erica Fradinger studying the effects of organophosphate pesticides on zebrafish development. He also assessed use of zebrafish as a model for testing chemical antidotes for organophosphate poisoning, in collaboration with Drs. Palmer Taylor and Zoran Radić at the University of California San Diego. Afterwards, he started his PhD at Harvard University where he joined the laboratory of Dr Andrew Kruse. There, Hayden studied the structural pharmacology and biochemistry of σ1 and σ2 receptors, a pair of enigmatic membrane proteins that are notable for their broad pharmacological profiles and promise as drug targets for several conditions. He joined our lab in July 2019 to work on the structural pharmacology of insect chemoreceptors, with the hope of applying the principles of structure-based drug design to characterise receptor-ligand interactions and develop novel, environmentally sustainable forms of agricultural pest control. In 2019, Hayden was awarded fellowhips from the Helen Hay Whitney Foundation and EMBO.
	Michael Shahandeh - Post-doctoral Fellow Michael obtained his Masters and PhD working in the Turner lab at the University of California, Santa Barbara. There he studied the proximate and ultimate causes of male mate choice evolution among Drosophila species using next generation sequencing technology. He joined our lab in Feb 2020 to investigate the molecular drivers of behavioral variation and divergence among generalist and specialist Drosophila species. Learn more about his scientific interests here.
	Suguru Takagi - Post-doctoral Fellow Suguru obtained his BEng from the Department of Applied Physics, University of Tokyo, where he studied the properties of shot noise in interferometry using power modulated laser beam. He then obtained his MS and PhD from the Department of Physics, the University of Tokyo, where he studied the circuit mechanisms and their molecular underpinnings of action selection in Drosophila melanogaster larvae, in collaboration with investigators in HHMI Janelia Research Campus and RIKEN BSI. He joined the lab in October 2019 to carry out cross-species comparisons of central olfactory circuits in drosophilids, supported by an EMBO Long-Term Fellowship and a Marie Sklodowska-Curie Individual Fellowship.
	Giovanna Zappia - Technician Giovanna obtained her MS in Pharmaceutical Biotechnology from the University of Milan, Italy, where she studied the role of ADAM10, a metalloprotease involved in the physiological functioning, brain development and pathogenesis of Alzheimer's disease. In 2010 she joined the Andrea Volterra's Lab in the Department of Fundamental Neuroscience at UNIL where she investigated the role of TNFα on the astrocytes in pathological conditions, particularly in experimental autoimmune encephalomyelitis (EAE), a mouse model of Multiple Sclerosis. She joined our group in Oct 2013.

The Benton lab is active in developing, optimising and documenting a number of diverse experimental methods we (and others) use. Please see below for links to published articles.

Bioinformatics

Hopf TA, Morinaga S, Ihara S, Touhara K, Marks DS and Benton R. Amino acid coevolution reveals three-dimensional structure and functional domains of insect odorant receptors. Nature Communications (2015) 6:6077 doi: 10.1038/ncomms7077 URL

We have collaborated with Debbie Marks' lab at Harvard to generate the first de novo three-dimensional models of insect Odorant Receptors using EVfold-Transmembrane. You can find all the resources for this method on the EVfold webpage. The accuracy of these models can be improved by increasing the number of ORs in the sequence alignments (currently just under 6000), so we would be happy to incorporate any OR sequence resources being generated by the community (please contact Richard Benton).

Histology and imaging

Saina M and Benton R. Visualizing olfactory receptor expression and localization in Drosophila. In Methods in Molecular Biology (2013) Vol. 1003 URL

Greg Jefferis' lab at the MRC-LMB has developed powerful tools for chemical-tag based in situ labelling; we've shown that these work well also in peripheral appendages:

Sutcliffe B*, Ng J, Auer TO, Pasche M, Benton R, Jefferis GSXE and Cachero S*. Second Generation Chemical Tags: Sensitivity, Versatility and Speed. Genetics (2017) doi:10.1534/genetics.116.199281 URL (*equal contribution)

Electrophysiology

Benton R and Dahanukar A. Electrophysiological recording from Drosophila olfactory sensilla. Cold Spring Harbor Protocols (2011) doi: 10.1101/pdb.prot5630 URL

Benton R and Dahanukar A. Electrophysiological recording from Drosophila taste sensilla. Cold Spring Harbor Protocols (2011) doi: 10.1101/pdb.prot5631 URL

Benton R and Dahanukar A. Chemosensory coding in single sensilla. Cold Spring Harbor Laboratory Press - Drosophila Neurobiology: A Laboratory Manual (2010) URL

Optical imaging

Silbering AF, Bell R, Galizia CG and Benton R. Calcium imaging in the Drosophila antennal lobe. Journal of Visualized Experiments (2012) 10.3791/2976 URL

Behaviour

Ramdya P, Schaffter T, Floreano D and Benton R. Fluorescence Behavioral Imaging (FBI) tracks identity in heterogeneous groups of Drosophila. PLOS ONE (2012) 7(11):e48381 URL

See also this resource page for FBI

Uhlmann V*, Ramdya P*, Delgado-Gonzalo R, Benton R and Unser M. FlyLimbTracker: an active contour based approach for leg segment tracking in unmarked, freely behaving Drosophila. PLOS ONE (2017) 12(4):e0173433 URL (*equal contribution)

Genetic tools in non-melanogaster drosophilids

We are currently generating many genetic & neurogenetic tools in Drosophila sechellia (as well as a few in Drosophila simulans) as part of our comparative neuroscience projects in the mel-sim-sec species trio. See our recent pre-print for more details on some of these efforts:

Auer TO, Khallaf MA, Silbering AF, Zappia G, Ellis K, Álvarez-Ocaña R, Arguello JR, Hansson BS, Jefferis GSXE, Caron SJC, Knaden M, Benton R. Olfactory receptor and circuit evolution promote host specialization. Nature. 2020 Mar;579(7799):402-408 URL

Reference brains for D. sechellia females and males, generated by Richard Benton and Greg Jefferis are available here

We are also interested in establishing community exchange for sharing ideas and reagents in genetic modification of non-melanogaster insect species. Please contact Richard Benton for more information.

Open Labware / 3D Printing

Through her work with TReND in Africa, Lucia Prieto-Godino has been involved in development of 3D design and printing for labs:

Baden T, Chagas AM, Gage G, Marzullo T, Prieto-Godino LL, Euler T. PLOS Biol (2015) 13(3):e1002086 URL

Maia Chagas A, Prieto-Godino L, Arrenberg AB and Baden T. The €100 lab: A 3D-printable open-source platform for fluorescence microscopy, optogenetics, and accurate temperature control during behaviour of zebrafish, Drosophila, and Caenorhabditis elegans. PLOS Biol (2017) 15(7):e2002702 URL

Some of the 3D printed object designs we use in the research in our group are available through Thingiverse

Datasets

Bulk RNA-Seq of control and pointed^RNAi antennae (GSE113997) from: Sensory neuron lineage mapping and manipulation in the Drosophila olfactory system". Chai P.C., Cruchet S., Wigger L., Benton R. Nature Communications (2019) 10 (1) p. 643.

Bulk RNA-Seq of control and peb-Gal4>UAS-p35 antennae (GSE128725) from: Prieto-Godino LL, Silbering AF, Khallaf  MA, Cruchet S, Bojkowska K, Pradervand S, Hansson BS, Knaden M and Benton R. Functional integration of “undead” neurons in the olfactory system. Science Advances (2020) doi:10.1126/sciadv.aaz7238

Quelques articles/emissions sur notre recherche - Some articles/broadcasts about our research

Understanding the fruit fly's nose (SNF/Latsis) (en anglais, sous-titré en français)

Une mouche alliée de la science (RTS - CQFD)

What fruit flies can teach us about the science of smell (Podcast at swissinfo.ch)

Sa majesté des mouches (Le Temps)

Rencontre avec Richard Benton (RTS - CQFD)

Im Kopf von Fruchtfliegen - Migros Magazin (auf deutsch)

The wisdom of the fly crowds (Ed Yong/National Geographic)

The world's first true aphrodisiac (NBC News)

Our European Research Councial project on the evolution of olfactory circuits (english / français)

Pseudo-pseudogenes (or "zombie genes") - RTS1 video report, Le Matin, 24heures (en français); Nature Podcast (in english)

An ant’s kiss may hide a sneaky form of communication - a comment in Science on our paper on trophallaxis and chemical communication in social insects; see also the Daily Mail and Wire