Testing of molecules that may regulate Glycogen Branching Enzyme (GBE1)

Overview
Updates

Dr. Escribá’ s focus in the last 15 years has been on discovering the dynamic role of the cellular membrane in the different functions of the cell. He is now Testing of molecules that may regulate Glycogen Branching Enzyme (GBE1).


GBE1 protein takes two forms: the so-called wild type (normal GBE protein) and Y329S, the mutation found in many APBD patients. We are producing both types modified in a way that can be purified in high amounts. We use insect cells to over express these proteins in a way that resembles the human ones. We have observed that the mutated Y329S form of the protein binds well to membranes, which decreases its activity, whereas the wild type does not bind and is therefore available for normal activity.


GBE1 protein takes two forms: the so-called wild type (normal GBE protein) and Y329S, the mutation found in many APBD patients. We are producing both types modified in a way that can be purified in high amounts. We use insect cells to over express these proteins in a way that resembles the human ones. We have observed that the mutated Y329S form of the protein binds well to membranes, which decreases its activity, whereas the wild type does not bind and is therefore available for normal activity.


We plan to distribute the protein to two other investigators, Or Kakhlon in Israel and Wyatt Yue in the UK, in order to investigate together the effect of different lipids on the structural and functional characterization of both forms of the enzyme. In addition, we have designed and are testing a number of molecules that may regulate GBE1-membrane interactions to increase the enzyme activity. Our goal is to find a potentially therapeutic molecule to be used in cellular and animal models of APBD and, eventually, in man. We know that triheptanoin is being studied for its effectiveness in reversing the symptoms associated with the condition. The results of this study will help in the designing of new molecules with potentially greater efficacy.

Goal: $100,000.00

$100.00 raised

Project donors:

$7600 donation by Coddon Family foundation