Funding outcome

Cohesinopathies are rare genetic disorders that affect children. Our focus is on how these disorders impact the nervous system and behavior. Children with cohesinopathies display intellectual disabilities, increased rates of seizures, attention deficit disorder, and autism spectrum disorders. Cohesinopathies occur due to mutations in genes that are part of the cohesin complex, which control the expression of downstream genes. There are no current treatments for cohesinopathies due to their complex nature and early onset. We are working to identify potential treatment targets by identifying genes that are affected by the cohesin complex members, which may contribute to neurological changes. In our Drosophila model of cohesinopathy, we found that stromalin, a cohesin complex member, affects memory in early development by reducing synaptic vesicles (SV). The SVs package neurotransmitters and are necessary for neurons' proper functioning and normal memory. We have identified a gene nep1 as a promising candidate that is responsible for stromalin's effects on neurons and is a promising target for treatment. Initial results show increasing nep1 levels can reverse memory and SV defects caused by stromalin deficiency. In addition, preliminary results show that stromalin deficiency in fruit flies leads to increased seizure rates and abnormal social behaviors. Further experiments will investigate the effects of stromalin and other cohesin complex members on these behaviors, and whether nep1 can rescue observed adverse effects. Understanding how these genes contribute to cohesinopathies opens doors for developing targeted therapies to improve the well-being of affected children.