Date of Award

Spring 5-2017

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Biology

First Advisor

Cuong Q. Diep, Ph.D.

Second Advisor

Daniel Widzowski, Ph.D.

Third Advisor

Robert Hinrichsen, Ph.D.

Abstract

Chronic Kidney Disease (CKD) is a major health problem, mainly due to the increasing rates of diabetes and hypertension. Current treatments are expensive and have severe limitations. Therefore, new approaches for treating kidney failure are needed. Unlike humans, zebrafish can regenerate their kidneys after injury using specialized stem cells. These stem cells express the lhx1a gene, which encodes a transcription activator that is important for making new kidney tissue. We recently showed that the lhx1a protein weakly dimerized with itself. The dimerization strength increased when the LIM domain of lhx1a was deleted. Others have shown deleting the LIM domain also causes lhx1a to become an active transcription activator. This suggests that the LIM domain negatively regulates dimerization and lhx1a’s activity. We hypothesize that molecules binding to lhx1a (at or outside of the LIM domain) could lead to lhx1a dimerization and activation. Such molecules could be used to activate kidney stem cells expressing lhx1a and promote kidney regeneration. Libraries of lariat peptides were generated and screened for interaction with lhx1a using the yeast-two-hybrid system. Out of 31 peptides candidates that were able to interact, one peptide has good sequence and can express in the yeast. This peptide can be used in future to screen its ability to enhance lhx1a dimerization and activation. Finding one peptide that could increase lhx1a activation might lead to enhance repairing kidney damage in human.

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