Tracking the aggregation knetics of mutant proteins in cells
A major area of research is defining how abnormal conformations of mutant proteins aggregate and interfere with the cellular machinery. One such protein we study is huntingtin, which when mutated causes Huntington's disease.
Huntington's disease is a devastating neurodegenerative disease often striking individuals mid-life. The disease is caused by an abnormally long polyglutamine repeat length near the amino-terminus of huntingtin. The extra glutamines cause the protein to change conformation, aggregate and form large aggregates known as inclusions.
We are building a profile of the aggregation process in cells as the protein converts from the normal monomeric state into aggregates; and how the steps of this process change the cell at the transcriptional and metabolomic level.
We also study the aggregation process of other proteins that also lead to disease, such as superoxide dismutase 1 in Motor Neuron Disease and a family of proteins that have polyalanine expansions in a manner analogous to the polyglutamine expansions, as well as other genes involved in these diseases including Fus and C9orf72.
Figure 1: We developed a flow cytometry method to separate cells with different aggregation states of proteins for further analysis
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