New mechanism points the way to breaking ribosome antibiotic resistance

In a article on Science Daily, research groups collaborated in researching in the dimerization of the bacterium Lactococcus Lactis by using cryo-electron microscopy. It involves a single protein Called the HPFlong. Which is capable of dimerizing on its own and pulling two copies of ribosomes together. When the ribosome is in dimerizing state it is unable of producing proteins . This leaves the ribosomes in a state of hibernation which allows for researchers to attack the cells with antibiotics. Researchers stated that protein HPFlong is present in all known bacteria which could result to the development of new generation of antibiotics.

I believe that this could help us with some current issues that involve antibiotic resistant bacteria. with these new results, we could use these methods to prevent bacteria from becoming more antibiotic resistant. this method will disable the microbial from creating a antibiotic resistant strand for the future generations of microbes.This will allow us to treat microbial infections more efficiently.



https://www.sciencedaily.com/releases/2017/09/170928084754.htm






https://www.eurekalert.org/pub_releases/2017-09/uog-nmp092517.php

"AAAAA Is for Arrested Translation"

In a post by Ruth Williams focusing on recent research results, a study conducted on the halt of protein translation found that multiple adenosine nucleotides in messenger RNA was the reason behind the interruption. The finding contradicted the idea that protein sequences were responsible. The importance behind the failure of the ribosome protein to translate the codon sequences of mRNA into amino acids lies on the fact that the mRNA and developing protein are degraded during the process.
Due to Rachel Green and her research team at Johns Hopkins University School of Medicine, it was found that there is a significance in the difference between mRNA sequences and associated amino acids. Bacterial ribosomes were found to halt on lysines in the presence of AAA codons as opposed to AAG codons. The research team, utilizing human cells, went on to find that reporter gene constructs with lysines encoded by AAA sequences had far less protein production then lysines encoded by AAG, as well as arginines encoded by AGG and CGA codons.
Two outcomes from this research were particularly important- bioinformatic analyses of vertebrate genomes proposed that the AAA codons are not favored evolutionary, and previously thought silent mutations may actually alter protein expression. The AAA sequence was thought to not be favored, being that the chance of lysines encoded by such a sequence was much lower than the chance of being encoded by AAG codons. The rejection of the silent mutation inference to instead be of greater importance, stemmed from mutating AAG codons to AAA codons and finding a decrease in protein expression. The opposite result was found from mutating AAA codons to AAG codons.
It is particularly interesting how failing to discover one tiny aspect of the translation process could later result in finding reasons behind translation failure. This may suggest that silent mutations are even more rare than previously thought, and that perhaps these mutations are simply misunderstood rather than inactive in many processes.

Using Zebrafish to Provide Genetic Answers

Susan Brooks, a medical geneticist of the Rutgers Robert Wood Johnson Medical School used zebrafish as a model organism to help identify the cause of a rare genetic disorder affecting a boy and his two uncles.  The boy suffered from seizures, fevers, slow growth, and poor head growth resulting in microcephaly.  Susan Brooks discovered that the peculiar disorder was most likely caused by a recessive mutation on the X-chromosome, as the boy's uncles shared similar symptoms.   These X-linked mutations can be carried by both males and females, but cause symptoms only in males with very few exceptions.

Scientists found a mutation carried by the affected males and their mothers, within a gene known as RPL 10.  It is located on the X-chromosome and encodes part of the ribosome, which is a vital piece of molecular equipment that is responsible for translating genetic code into proteins.  Scientists used zebrafish to test the effect of the mutation.  Duke University researchers led by Erica Davis from the Center for Human Disease Modeling displayed that the diminishing expression of the RPL 10 gene caused organisms to develop notably smaller heads, or the fish version of microcephaly.

The image above displays the effect of the expression of the RPL 10 gene (top), 

versus the suppressed expression of the RPL 10 gene (bottom) in the heads of zebrafish.

Unfortunately, identifying the likely cause of the disorder does not ensure a cure for the boy and his two uncles, but it is the first step for future research in developing treatments.  Erica Davis stated, "This was a one-of-a-kind family affected by a disorder that no one had ever seen before, but they are not alone.  The best way of finding answers for these families is for clinicians and model organism researchers to join forces."  Zebrafish and humans share approximately 70% of protein-coding genes, and 84% when the genes known to be associated with disease are considered.  Zebrafish are a very important model organism in genetics.  They are cheaper to maintain and grow faster than mice.

This article caught my eye immediately, as I conducted research with Dr. Brian Rogerson last semester using zebrafish.  We analyzed AICD (Activation-induced cytidine deaminase) levels in young and old zebrafish, which is an enzyme known to be responsible for the mutation of antibody genes.  Due to being familiar with the use of zebrafish as a model organism, I am very interested in learning about how they are being used in other studies.  I find it fascinating that the diminished expression of the RPL 10 gene had a very similar impact on zebrafish, as it did on humans.  It opens up an unlimited number of possibilities in the future regarding the use of zebrafish in studying human disease.

Article [1]: http://medicalxpress.com/news/2014-10-family-zebrafish-genetic.html 
Related Article: http://www.genetics-gsa.org/news/templates/?a=210&z=1