John Manak, a Professor in the Department of Biology, received a Summer 2026 Interdisciplinary Research Grant from the Obermann Center for Advanced Studies to study Intellectual disability (ID). ID is a common neurodevelopmental disorder characterized by significant limitations in learning, memory, and problem-solving as well as social interaction and communication. Using health databases and fruit fly genetic approaches, Dr. Manak will work with Dr. Benjamin Darbro from the Stead Family Department of Pediatrics to identify genes associated with ID. The project will be funded by a Laura Spelman Rockefeller grant.

See below for more details on the project taken from the Obermann Center for Advanced Studies website.

Leveraging Fruit Fly Genetics and Clinical Genetic Testing to Help Identify Genes Associated with Intellectual Disability
Intellectual disability (ID), a remarkably common neurodevelopmental disorder in the population (2–3%), is characterized by significant limitations in learning, memory, and problem-solving, as well as difficulties in social interaction and communication. While genetic factors play a large role in the cause of ID, and a variety of candidate genes have been identified, the proof that these genes actually contribute to ID is notably lacking in part due to the inability to screen the genes in a model system that allows for an efficient, high-throughput approach. Moreover, given that complex neurological disorders such as ID have a complex genetic underpinning, novel approaches to identifying new candidate genes are warranted.

This project seeks to address both of these shortcomings: it will leverage the expertise of a board-certified clinical and molecular genetic pathologist-scientist with extensive patient DNA analysis (Dr. Darbro), who will mine largescale patient databases of individuals with ID in order to discover previously unidentified ID genes. The approach will move beyond gene discovery in research-only cohorts and connect candidate gene selection to real-world clinical testing data from a large, diverse pediatric patient population. The project will also leverage the expertise of a geneticist (Dr. Manak) with over 25 years of experience using fruit fly models of human disease (including neurodevelopmental disorders) to functionally validate the genes that Dr. Darbro identifies. Once the fly homologs of the human genes are identified, Dr. Manak will utilize a gene-silencing approach to “knock down” the identified genes in the brains of the fruit fly, followed by high-throughput analysis to assess whether these “gene knockouts” result in clinical features consistent with those of ID. This proposal will lead to concrete outcomes (i.e., better diagnostic yields) that ultimately translate scientific discovery into better guidance and support for patients and their caregivers.

Co-directors: John Manak (Biology, CLAS, UI) and Benjamin Darbro (Pediatrics, Carver College of Medicine, UI)

*This project will be funded by a Laura Spelman Rockefeller grant.