Jonnathan Marin
Cohort: 2020

Cystic Fibrosis (CF) is a hereditary disease caused by loss of function mutations in the CFTR anion channel, which is responsible for HCO3- and Cl- secretion in airway epithelia. As is also the case for other channelopathies, current treatment options do not address functional deficiency for all mutations. The field of molecular prosthetics offers a unique and broad treatment option for this class of diseases. Our group has previously shown that a molecular prosthetic candidate, Amphotericin B (AmB), a polyene macrolide natural product, can restore HCO3- secretion in cultured CF airway epithelial due to its capability of self-assembling into a multimeric ion channel. Preliminary data from our group, in addition to biological inspiration, suggest that the ion-selectivity of AmB could be tuned through synthetic modifications. I aim to synthesize targeted derivatives of AmB, modified on the pore-lining region of the channel, and study the ion selectivity and other electrophysiological parameters. These studies will enable a better understanding of the underlining small molecule base ion channel function and corresponding therapeutic potential for various channelopathies.