Jun
03

Post #1: First Experiment Started!

Hi everyone! I am back in Dr. Allison’s lab and I have begun working on my first set of experiments this summer. With this specific experiment, I will be looking at the intracellular localization patterns of two TR-a1 mutants that have been previously linked to resistance to thyroid hormone syndrome (RTH), an autosomal recessive disorder in which the body’s tissues are resistant to the effects of thyroid hormone. Patients with RTH usually exhibit hypothyroidism-like symptoms such as goiter, hearing loss, short stature, and bone deformations. Unlike hypothyroidism, however, patients also exhibit high levels of thyroid hormone in the bloodstream. Research suggests that defects in the signaling of thyroid hormone receptor, caused by a number of mutations in the protein, might be responsible for the disorder.

The two mutants that I will be studying  have been found in the tissues of patients with the condition. Mutant 1 has a residue substitution in one of the protein’s nuclear export sequences (NES-H12), while Mutant 2 has premature stop codon placed in this same region. This sequence binds to a number of proteins known as ‘exportins’, that regulate the export of the receptor from the nucleus into the cytoplasm.

I plan to tag these mutant TR-a1 variants with green-fluorescent protein (GFP) and express them in a human cell line. Then, by observing the cells under fluorescence microscopy, I will be able to notice if these mutant receptors show differences in nuclear export when compared to the wild type receptor. Stay tuned for my results!

 

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