Vieta: R406
Neurodevelopmental disorders: from genes to mechanisms
Abstract:
Intellectual Disability (ID) and Autism Spectrum Disorder (ASD) are prevalent and often co-occurring neurodevelopmental disorders characterized by deficits in cognitive and adaptive function. These disorders pose significant challenges for affected individuals and their families. Currently, no treatments are available to address the cognitive deficits, and the underlying mechanisms remain poorly understood. Advanced sequencing technologies have identified over 1,800 monogenic causes of ID/ASD, and the affected genes serve as an entry point for investigating molecular mechanisms and identifying therapeutic targets. To study these mechanisms efficiently and on a large scale, we employ the fruit fly, Drosophila melanogaster, an effective model organism with strong genetic and biological parallels to humans. Our work has demonstrated that Drosophila models with mutations equivalent to those found in individuals with ID/ASD often present deficits in habituation, a fundamental and conserved form of learning that underpins higher cognitive functions. In line with the conserved nature of habituation mechanisms across species, our findings indicate that habituation deficits in Drosophila can predict the absence of habituation in genetically matched individuals with ID/ASD. Given its specificity to ID/ASD and its cross-species compatibility, habituation emerges as a valuable readout for investigating the impact of ID/ASD genes and genetic variants on cognitive function, with promising translational potential for clinical applications. Our laboratory is now leveraging Drosophila habituation as a preclinical platform to (1) investigate neuronal mechanisms underlying cognitive deficits in ID/ASD and identify potential therapeutic targets; (2) support diagnostics and provide functional insights into novel, patient-specific ID/ASD mutations; and (3) expand understanding of molecular mechanisms beyond the brain and neurons, exploring brain-body interactions and identifying non-neuronal therapeutic targets.
Biosketch:
Dr. Michaela Fencková earned her Ph.D. in 2012 from the University of South Bohemia. She then pursued a postdoctoral fellowship at Radboud University Medical Center in the Netherlands, where, under the mentorship of Prof. Annette Schenck, she gained expertise in Drosophila models of neurodevelopmental disorders. She gained skills in CRISPR/Cas9 editing and modeling of patient-specific mutations during a subsequent postdoctoral position in Prof. Daan van Aalten’s laboratory at the University of Dundee, United Kingdom. Dr. Fencková then returned to her alma mater to establish the Laboratory of Neurogenetics, supported by funding from the Czech Science Council and prestigious ERC-CZ and EMBO Installation Grant programs. She has received the national L’Oréal-UNESCO For Women in Science Award and is a member of the FENS-Kavli Network of Excellence and the FENS Committee for Higher Education and Training.