Group Botond Roska

Visual circuits: structure, function, and repair

Vision is a key sense for humans, and dysfunction of the visual system leads to visual handicap or blindness. My laboratory aims to find ways to repair visual dysfunction by investigating the function of the retina, thalamus, and cortex at the level of cell types and circuits, and using the acquired knowledge to understand disease mechanisms and to develop treatments.

Our experimental approach is inter-disciplinary: We combine physiological, molecular, viral, and computational approaches to reveal the structure and function of visual circuits. We use molecular techniques to genetically identify cell types in the network and label them using transgenic or viral technologies. The connections between labeled cells are revealed using trans-synaptic viruses. We then study the function of a genetically isolated circuit with physiological and imaging tools. Finally, we use computational methods to predict the behavior of an isolated circuit under natural conditions.

We combine the insights from our basic circuit investigations with human genetics to understand disease mechanisms and we use viral vectors to develop cell-type-targeted gene therapy to treat visual dysfunction. Currently we are focusing on cell-type-targeted optogenetic therapy.

Group Members

Group Leader: Botond Roska

Postdoctoral fellows

Arjun Bharioke

Tamas Dalmay

Alex Fratzl

Alvaro Herrero Navarro

Atsuki Hiramoto

Mohammad Khani

Katja Kolar

Georg Kosche

Akos Kusnyerik

Veronica Moreno-Juan

Rei Morikawa-Kanamori

Fiona Muellner

Martin Munz

Dasha Nelidova

Helene Schreyer

PhD students

Temurkhan Ayupov

Miklos Boldogkoi

Gasser Elmissiery

Alissa Muller

Tiago Rodrigues

Stefan Spirig

Hannah Stabb

Technical/Research associates

Serena Curtoni

Ilaria Gregorio

Nicole Ledergerber

Dimitri Rey

Giuseppe Vaccaro

Ophthalmology resident researcher

Stefan Futterknecht

Selected Journal Articles

Partial recovery of visual function in a blind patient after optogenetic therapy: Sahel JA, Boulanger-Scemama E, Pagot C, Arleo A, Galluppi F, Martel JN, Degli Esposti S, Delaux A, de Saint Aubert JB, de Montleau C, Gutman E, Audo I, Duebel J, Picaud S, Dalkara D, Blouin L, Taiel M, Roska B.; Nature Medicine. 2021
Cell Types of the Human Retina and its Organoids at Single-Cell Resolution: Cameron S. Cowan, Magdalena Renner, Martina De Gennaro, Brigitte Gross-Scherf, David Goldblum, Yanyan Hou, Martin Munz, Tiago M. Rodrigues, Jacek Krol, Tamas Szikra, Rachel Cuttat, Annick Waldt, Panagiotis Papasaikas, Roland Diggelmann, Claudia P. Patino-Alvarez, Patricia Galliker, Stefan E. Spirig, Dinko Pavlinic, Nadine Gerber-Hollbach, Sven Schuierer, Aldin Srdanovic, Marton Balogh, Riccardo Panero, Akos Kusnyerik, Arnold Szabo, Michael B. Stadler, Selim Orgül, Simone Picelli, Pascal W. Hasler, Andreas Hierlemann, Hendrik P.N. Scholl, Guglielmo Roma, Florian Nigsch, Botond Roska; Cell. 2020
Restoring light sensitivity using tunable near-infrared sensors: Dasha Nelidova, Rei K. Morikawa, Cameron S. Cowan, Zoltan Raics, David Goldblum, Hendrik P. N. Scholl, Tamas Szikra, Arnold Szabo, Daniel Hillier, Botond Roska; Science. 2020
Targeting neuronal and glial cell types with synthetic promoter AAVs in mice, non-human primates and humans.: Jüttner J, Szabo A, Gross-Scherf B, Morikawa R, Rompani S, Hantz P, Szikra T, Esposti E, Cowan C, Bharioke A, Patino-Alvarez C, Keles Ö, Kusnyerik A, Azoulay T, Hartl D, Krebs A, Schübeler D, Hajdu R, Lukats A, Nemeth J, Nagy Z, Wu KC, Wu RH, Xiang L, Fang XL, Jin ZB, Goldblum D, Hasler P, Scholl H, Krol J, Roska B; Nat Neurosci. 2019
Whole-Brain Functional Ultrasound Imaging Reveals Brain Modules for Visuomotor Integration: Émilie Macé, Gabriel Montaldo, Stuart Trenholm, Cameron Cowan, Alexandra Brignall, Alan Urban, and Botond Roska (2018); Neuron 100, 1241–1251
How Diverse Retinal Functions Arise from Feedback at the First Visual Synapse: Antonia Drinnenberg, Felix Franke, Rei K. Morikawa, Andreas Hierlemann, Rava Azeredo da Silveira and Botond Roska (2018); Neuron. 2000; 27: 513-523
Restoring Vision: Roska B & Sahel JS (2018); Nature 2018 May; 557(7705):359-367
Virus stamping for targeted single-cell infection in vitro and in vivo.: Schubert R, Trenholm S, Balint K, Kosche G, Cowan CS, Mohr MA, Munz M, Martinez-Martin D, Fläschner G, Newton R, Krol J, Scherf BG, Yonehara K, Wertz A, Ponti A, Ghanem A, Hillier D, Conzelmann KK, Müller DJ*, Roska B* (2018); Nature Biotechnology 2018 Jan;36(1):81-88
Causal evidence for retina-dependent and -independent visual motion computations in mouse cortex.: Hillier D, Fiscella M, Drinnenberg A, Trenholm S, Rompani SB, Raics Z, Katona G, Juettner J, Hierlemann A, Rozsa B, Roska B (2017); Nature Neuroscience 2017 Jul;20(7):960-968
Different Modes of Visual Integration in the Lateral Geniculate Nucleus Revealed by Single-Cell-Initiated Transsynaptic Tracing.: Rompani SB, Müllner FE, Wanner A, Zhang C, Roth CN, Yonehara K, Roska B. (2017); Neuron. 2017 Feb 22;93(4):767-776
Congenital Nystagmus Gene FRMD7 Is Necessary for Establishing a Neuronal Circuit Asymmetry for Direction Selectivity.: Yonehara K, Fiscella M, Drinnenberg A, Esposti F, Trenholm S, Krol J, Franke F, Scherf BG, Kusnyerik A, Müller J, Szabo A, Jüttner J, Cordoba F, Reddy AP, Németh J, Nagy ZZ, Munier F, Hierlemann A, Roska B (2016); Neuron. 2016 Jan 6;89(1):177-93
Single-cell-initiated monosynaptic tracing reveals layer-specific cortical network modules.: Wertz A, Trenholm S, Yonehara K, Hillier D, Raics Z, Leinweber M, Szalay G, Ghanem A, Keller G, Rozsa B, Conzelmann KK, Roska B. (2015); Science. 3;349(6243):70-4
Transcriptional code and disease map for adult retinal cell types.: Siegert S, Cabuy E, Scherf BG, Kohler H, Panda S, Le YZ, Fehling HJ, Gaidatzis D, Stadler MB, Roska B (2012); Nat Neurosci. 15(3):487-95
Spatially asymmetric reorganization of inhibition establishes a motion sensitive circuit.: Yonehara K, Balint K, Noda M, Nagel G, Bamberg E, Roska B (2010); Nature 469:407-10
Genetic reactivation of cone photoreceptors restores visual responses in retinitis pigmentosa.: Busskamp V, Duebel J, Balya D, Fradot M, Viney TJ, Siegert S, Groner AC, Cabuy E, Forster V, Seeliger M, Biel M, Humphries P, Paques M, Mohand-Said S, Trono D, Deisseroth K, Sahel JA, Picaud S, Roska B (2010); Science 329:413-7
Characterization of microRNAs induced by light adaptation in mouse retina reveals rapid turnover as a common property of neuronal microRNAs.: Krol J, Busskamp V, Markiewicz I, Stadler MB, Ribi S, Duebel J, Oertner TO, Schübeler D, Schratt G, Fehling HJ, Richter J, Bibel M, Roska B*, Filipowicz W* (2010) *shared corresponding authors; Cell 141:618-31
Genetic address book for retinal cell types.: Siegert S, Gross Scherf B, Del Punta K, Didkovsky N, Heintz N, Roska B (2009); Nature Neurosci 12:1197-1204
Light-activated channels targeted to ON bipolar cells restore visual function in retinal degeneration.: Lagali PS, Balya D, Awatramani GB, Münch TA, Kim DS, Busskamp V, Cepko CL, Roska B (2008); Nature Neurosci 11:667-675

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