Donders Institute for Brain, Cognition and Behaviour
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Theme 3: Plasticity and Memory

Drosophila Models of Brain Disorders

Donders-PLASTICITY-MEMORY-screen thema 3Our research focuses on dissecting molecular networks and mechanisms underlying human brain function and disease.

Mutations in more than 400 genes are known to give rise to Intellectual Disability (ID), providing an exciting starting point to study this problem. Accumulating evidence suggests that some of these genes ("ID genes") operate together to control specific aspects of nervous system development and function. However, the function of most ID genes is unknown or poorly characterised at present. We aim at providing functional data for all ID genes and at systematically identifying their molecular connections.

In order to be able to investigate the large number of genes, we use a powerful genetic model organism, the fruitfly Drosophila melanogaster. In flies, genes can be manipulated specifically in neurons with relative ease, and consequences for neuronal architecture, function and cognitive behaviour of the fly, such as learning and memory, can be studied and compared. Furthermore, we use the gained knowledge on ID gene function and the fruitfly as a model to search for genetic and chemical modifiers of fly "ID" phenotypes. This research identifies novel candidate genes and potential medication for humans.

Recent data including our own indicate that some forms of ID indeed result from reversible inabilities of the nervous system, raising serious hope that impaired cognition can be treated. Beyond the expected fundamental insights into molecular pathways that wire the brain, our research also aims at significantly contributing to such developments.

Whereas these projects primarily aim to understand the neuronal basis and molecular underpinnings of their specific human disorders, they also serve as pilot projects for our systematic approaches to ID, as they continuously improve our knowledge on ID-relevant fly phenotypes. We also become increasingly interested in Autism, Attention deficit hyperactivity (ADHD), Schizophrenia and language disorders, and into the arising theme that the genetics and neurobiology of these disorders significantly overlap with each other and with Intellectual disabilities.

Name: Annette Schenck
Telephone: 024-3610868
Visiting address: Department of Genetics, Radboud University Nijmegen Medical Center
Geert Grooteplein Zuid 10, route 855
6525 GA Nijmegen
The Netherlands
Postal address: Department of Genetics, Radboud University Nijmegen Medical Center
P.O. Box 9101 / 855
6500 HB Nijmegen
The Netherlands
Key publications
  • Kleefstra T, Kramer JM, Neveling K, Willemsen MH, Koemans TS, Vissers L, Wissink-Lindhout W, Fenckova M, van den Akker WMR, Nadif-Kasri N, Nillesen WM, Prescott T, Clark RD, Devriendt K, van Reeuwijk J de Brouwer APM, Gilissen C, Zhou H, Brunner HG, Veltman JA, Schenck A§ and van Bokhoven H§ Disruption of a novel EHMT1-associated chromatin modification module causes intellectual disability. Am J Human Genetics, 2012, 91(1):73-82.
  • Koolen DA, Kramer JM, Neveling K, Nillesen WM, Moore-Barton HL, Elmslie FV, Toutain A, Amiel J, Malan V, Tsai ACH, Cheung, SW, Gilissen C, Verwiel ETP, Martens S, Feuth T, Bongers EMH, de Vries P, Scheffer H, Vissers LEL, de Brouwer APM, Brunner HG, Veltman JA, Schenck A§, Yntema HG§, de Vries BBA§ Mutations in the chromatin modifier KANSL1 cause the 17q21.31 Microdeletion Syndrome. Nature Genetics, 2012 doi:10.1038/ng.2262; Epub ahead of print Apr 29.
  • Kramer JM, Kochinke K, Oortveld MAW, Marks H, Kramer D, de Jong EK, Asztalos Z, Westwood JT, Stunnenberg HG, Sokolowski MB, Keleman K, van Bokhoven H§ and Schenck, A§. Epigenetic regulation of learning & memory by Drosophila EHMT/G9a. PLoS Biol. 2011, 9(1): e1000569.
  • Zweier C, de Jong EK, Zweier M, Orrico A, Ousager LB, Collins AL, Bijlsma EK Oortveld MAW, Ekici AB, Reis A, Schenck A and Rauch A. CNTNAP2 and NRXN1 are mutated in recessive, severe mental retardation resembling Pitt-Hopkins syndrome and target a common synaptic protein in Drosophila. Am J Human Genetics, 2009, 85(5):655-66.
  • Schenck A, Goto-Silva L, Collinet C, Rhinn M, Giner A, Habermann B, Brand M, and Zerial M. The endosomal protein APPL1 mediates Akt substrate specificity and cell survival in vertebrate development. Cell, 2008, 133(3): 486-497.

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Theme 3:
Plasticity and Memory

Research Group
Drosophila Models of Brain Disorders

Principal Investigator
Prof. dr. A. Schenck

Group members

Dr. Michaela Fencková
Dr. Kevin Lüthy

PhD candidates
Laura Blok
Marina Boon
Mireia Coll-Tané
Ilse Eidhof
Benjamin Harich
Adela Long
Boyd van Reijmersdal
Lara van Renssen
Human Riahi Asl

Research technician
Irene Janssen

Update Oct 2020