HOW CAN WE MOVE OUR WORK
FROM BENCH TO BEDSIDE?
Patients
Research
Glia in Congenital Disorders of Glycosylation
Just as proper function of a community of people is dependent on clear communication, the human body requires trillions of neighboring cells to associate and talk with one another to stay healthy. This association is facilitated by specialized proteins and lipids at the boundary of our cells, named glycoproteins and glycolipids, respectively. The prefix “glyco” comes from the decoration of these proteins and lipids with small sugar groups, called glycans. Without these sugar groups, there is defective cell-cell signaling, loss of tissue integrity, and organ failure.
OPEN PROJECTS
Role of Alg8 in glial
development and function
Generating "humanized" zebrafish
to model ALG8 CDG
Drug screens to drive repair
in ALG8 CDG
Neurological dysfunction is a common symptom in patients with congenital disorders of glycosylation (CDGs). Mutations in ALG8 result in a CDG associated with epilepsy and reduced brain activity. As glia associate closely with neurons to regulate brain activity, we hypothesize that neurological deficits in ALG8-CDG result from failed glia-neuron communication. In the Ackerman lab, we leverage zebrafish, the smallest genetically tractable model organism, to understand the cellular basis of neurological defects in ALG8-CDG. Zebrafish are optically transparent, allowing direct imaging of neural circuit structure/function in an intact, behaving organism. Furthermore, they have functionally conserved genes, neuron, and glial cell types. Finally, they are highly amenable to drug screens, allowing for rapid translation from bench to bedside. This patient-driven research is made possible through the support of Project GRACe and CDG CARE (read more below).
Timeline
September 15:
Project GRACe starts!
November 1:
CRISPR injections begin!
Quarter 1 Update: Meet the Team
Mika Matsuguma,
MSc
Mika received her MSc. in Genetics and Molecular Biology from the State University of Campinas, Brazil, where she studied the molecular mechanisms that guide early embryonic development. Mika joined the Ackerman lab in July of 2022, where she has quickly leveraged her skills to study the brain. Mika is the soul of the Project GRACe team- dedicating the last 2 months to the development of CRISPR/Cas9 techniques to generate new Alg8 models in zebrafish.
Left: Mika at Pierre Marquette for the WashU Genetics Retreat
Right: Mika injecting CRISPRs to target zebrafish Alg8!
