Funded Research for 2020 by FPWR UK

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This year FPWRUK are helping fund a project looking at ‘How is the Epitranscriptomic Signature of Active AGRP Neurons disrupted in PWS?’.  This project is being lead by Donna Lehman at the University of Texas Health Science Centre.

AGRP neurons are found in the hypothalamus and when working correctly function to signal being full and being hungry.  These neurons are thought to be dysfunctional in those with PWS. 

Lets try to explain what will be happening in this research………

DNA is basically a huge recipe book with thousands and thousands of recipes (think of each recipe as a gene) to make different proteins.  Proteins, are the ‘workhorses’ of the body. Nearly every function in the human body – both normal and disease-related – is carried out by one or many proteins.  DNA lives in the nucleus of a cell but the machinery to make proteins is located outside the nucleus so in order to make these essential proteins, we need to make a copy of the recipe that can travel outside the nucleus.  This copy is messenger RNA, or mRNA for short and acts as the intermediary code that cells use to transfer information stored in DNA into a set of instructions that cells can easily read for making proteins.

A transcriptome is the full range of mRNA molecules expressed by an organism’s DNA.  It was later discovered that these RNA transcripts are modified by cells.  These modifications became known as the epitranscriptome. Enzymes can add or remove methyl marks from mRNA transcripts, which control the fate of mRNA, and thus protein production.  The study of the eiptranscriptome has become an interesting area in the treatment of disease and may provide targets for drug treatment.  For example, the epitranscriptomic code—the number and location of chemical modifications across a cell’s RNA—is seriously different in those with certain cancers.

This project will use human hypothalamic hunger neurons (AGPR) created from stem cells with or without the PWS gene, SNORD116, to provide the first glimpse into how the loss of SNORD116 might be affecting the epitranscriptome of those with PWS.