2018 Nobel Prize Winners for Their Work with Proteins and Enzymes

   
      Last week was a momentous occasion for many people in the field of research, as the Nobel's Prizes for each category were announced. Many people waited and watched, riddled with anticipation, as each winner was announced, and by Monday there were a grand total 12 Nobel Laureates recognized for their outstanding achievements. Among the 12 Nobel prize winners, there were 3 laureates of particular interest that contributed further to the knowledge and understanding of biology and genetic evolution.
     Dr. Frances H. Arnold was the first Nobel laureate to be recognized for her work with directed evolution of enzymes. Dr. Arnold pioneered the first bio-engineering method in 1990 called directed evolution. Directed evolution is a method that introduces random mutations into a gene, which is then inserted into an enzyme and is used as a template to produce a catalyst for desired reactions. Directed evolution has been used to produce chemicals that are safer for people as well as the environment. Chemicals such as bio-fuels, medicine, laundry detergents and more have been created using this process. Dr. Arnold has used evolution to her advantage and in an article in the NY Times she stated "I copied nature’s inventions, this wonderful process of evolution, to breed molecules like you breed cats and dogs.”

       Dr. George P. Smith and Sir Gregory P. Winters shared the 2018 Nobel Prize with Dr. Arnold for their work with bacteriophages. Dr. Smith, from University of Missouri, was looking to identify unknown genes using peptides and bacteriophages. In order to identify the unknown genes, Dr. Smith would insert genes into bacteriophages, which would then express the protein on the surface. Dr. Smith watched these antibodies to see if they would interacted with the proteins and identifying them as a pathogen. The different types of antibodies only fit specific types of proteins, and once an antibody identifies a protein, scientists can then deduce the identity of the unknown gene.
     Sir Gregory P. Winters, from MRC Laboratory of Molecular Biology UK, went a step further and used Dr. Smith's research to produce more efficient and prolific antibodies. Instead of inserting an unknown gene into a bacteriaphage, Dr. Winters inserted the bacteriapages with antibodies and selected the ones that bound the most effectively. He then repeated the process several times to produce powerful disease fighting antibodies. According to the NY Times, "the first antibody drug developed this way, adalimumab, which is sold under the brand name Humira" (Chang, 2018). This drug was used to fight diseases like rheumatoid arthritis, psoriasis and inflammatory bowl disease. In addition to his drug synthesis, Dr. Winter also used this technique to produce efficient antibodies that could shrink tumors in the human body. In order to do this, Dr. Winter tweaked a mouse antibody, using the same technique, and injected that antibody into a patient with a deadly tumor. The tumor shrank successfully and the patient suffered from no side effects. The shrunken tumor was the first ever human test to see if this procedure could be used for the public health.

Fighting Antibiotic Resistance with CRISPR

          Researchers out of the University of Wisconsin-Madison are working on a novel way to solve the growing danger of antibiotic resistant bacteria. Their work is focused on one of the most prominent and dangerous of these bacteria, Clostridium difficile. Due to the overuse and over prescription of antibiotics this strand of bacteria, along with others, have gained resistances to nearly all available treatment drugs. The team is attempting to combat this resistance through the use of a probiotic infused with bacteriophages carrying a variant of the CRISPR system. The probiotics would protect the bacteriophages which would ultimately emerge and target the Clostridium difficile within the gut of the patient. The injected CRISPR complex would then target the bacteria's DNA, promoting cell death. This research adds yet another potential life saving use of CRISPR to a list that has been growing steadily since its discovery.

Customizing Viruses to Fight Selected Bacteria

A team from the Massachusetts Institute of Technology (MIT) has recently developed a "mix-and-match" system that allows the genomes of bacteria-eating viruses to be more easily manipulated to target specific bacteria. This team has designed a system of taking genes from bacteriophages and swapping them in and out to produce functional phages that have new properties and can be used to target specific bacteria. The idea of using viruses to kill disease-causing bacteria is relatively old, but this new system is much less expensive and not as time consuming. 

For their study, the team at MIT used bacteriophages from the family known as T7, which naturally attack E. coli. The bacteriophages, as well as many other bacteriophages, are made of a head region with a tail that they use to attach to their target bacteria cell. By swapping genes in the tails of the bacteriophages, which dictates the target of the bacteriophage,  they were able to create several phages that would target many different types of bacteria. They were then able to find the gene sequences that code for the tail of the T7 family, and from these sequences, develop a new way to genetically engineer the T7 genome. This new process involved inserting the viral genome into a yeast cell, which made the genome more accessible for gene-swapping. This overall process in much faster, easier, and less expensive than alternatives and is revolutionary in the research of this topic. 

The team now hopes these studies and developments can be used in a variety of different ways. The new system could be used to more easily "edit" mixed populations of bacteria, such as the bacteria found in the digestive tract, and be effective in eliminating harmful bacteria in areas where both harmful and helpful bacteria exists. It could also be helpful in other applications, such as spraying crops and disinfecting foods. 

This article is very interesting because it shows an important application of genetics. It shows how knowledge of genomes and the properties of certain genes can be used in a variety of ways, including developing viruses that kill certain types of bacteria. It is amazing to think these bacteriophages can be so easily manipulated for our use, simply because we have an understanding of their genome and how they detect the cells they want to attack. 

For more interesting articles on how viruses can be used for fighting bacteria click here

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Viruses that Can Fight Bacteria?!

  Scientists have already studied and tested viruses to eat bacteria, however, targeting specific bacteria is takes time and is costly. According to Timothy Lu from MIT, he and his team have created a new system that can swap genes in order to customize viruses to eat any pathogenic bacteria. Lu says, "These bacteriophages are designed in a way that's relatively modular. You can take genes and swap them in and out and get a functional phage that has new properties."
   One goal of this new system is to assist in killing bacteria that do not have any effective antibiotics. Another is to perhaps assist in other human functions like digestion. In the human digestive tract, there is bacteria to help with digestion but also others causing disease, the they hope to see some "edits" in the bacteria to keep the disease causing bacteria to a minimum so that the use of antibiotics is reduced. Antibiotics can not specify which bacteria are to be removed, resulting in targeting both the friendly and disease causing bacteria.
  For the study, the team chose a bacteriophage T7 that attacks Escherichia coli. The phage is made up of a head and a tail, the tail is what attacks the target. The team substituted genes in the tail of T7 that resulted in a phage that could target a several different types of bacteria.  The team believes they have created a more simple and quick process through this. The researches were able to redesign the tail of T7 by researching new sequences that are similar for the tail of T7. Once the structures were found, swapping them out was not as labor induced as they had thought. They also found that putting the genome into a yeast cell made it easier for the gene-swap.
   The MIT team showed that their study could help changed phages to specifically attack strains of Gram-negative bacteria, which has few antibiotics against it. 
  David Bikard from the Institut Pasteur in Paris says, "This is a big step in the development of phage therapies with predictable outcomes and a good demonstration of what synthetic biology approaches will bring to medicine in the near future."
I think this article was interesting in the fact that we can use viruses, which we all hates, to fight bacteria, another thing we all hate (mostly). I'm looking forward to see what advantages that will bring us in the future and how it can better our health. 

  
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The use of Bacteriophages in combating antibiotic resistant bacteria.

Phage therapy uses bacteriophages in order to treat specific bacterial infections without harming the human microbiota. Lytic bacteriophages attach to specific bacteria, penetrate and inject their genetic material, force the bacteria to manufacture products for a new generation of viruses and finally lyse the infected bacteria to release the newly made phages.
Research for this type of treatment originated in the Soviet Union at a time when they had no access to the antibiotics being produced in the west, but it is now been revised in order to tackle the growing concern of antibiotic resistant bacteria.
The issue that lies with broad-spectrum antibiotics is that they destroy an extensive scope of bacterial strains. Bacteriophages are able to attack a single strain or species of bacteria without destroying others that may prove useful for the balance of the human micriobiota. Unlike antibiotics, when bacteria develop mechanisms to prevent the penetration of these viruses, researchers are always able to change the type of bacteriophages being applied to a patient.
Researchers are also looking into creating their own synthetic bacteriophages that would only kill antibiotic resistant bacteria.

http://www.nature.com/news/phage-therapy-gets-revitalized-1.15348   main article
http://www.the-scientist.com/?articles.view/articleNo/41097/title/Bacteriophage-Boom-/
http://phages.org/   helpful

New Virus Already Inside Us?

     Genetic researchers from around the country have discovered a new virus known as a bacteriophage, that may be present in at least half of the population. This type of virus (named crAssphage) infects bacteria, and is suspected to live in the human gut. According to the LiveScience article, it was discovered when many researchers identified it in fecal samples from multiple different subjects. 

     Although not much is known about the virus to date, Dr. Amesh Adalja, an infectious disease physician at the University of Pittsburg and a representative of the Infectious Disease Society of America, believes this may play a role in common conditions that affect humans around the world. She cited obesity and cancer as such possibilities. Understanding this new finding may be the key to unlocking a cure to the conditions that have plagued humanity since it's beginnings.

     Robert Edwards, a bioinformatics professor at San Diego State University and one of the researchers who worked on the study, feels that not enough information about the virus has been discovered to make such concrete conclusions. Edwards and his fellow researchers have not yet been able to replicate or photograph the virus, although they have identified crAssphage via it's DNA sequence. However researchers look at this new discovery, it adds helpful insight to the world of microbes and human health. 

Could bacteriophages transfer antibiotic resistance genes from environmental bacteria to human-body associated bacterial populations?

Researchers from the University of Barcelona, Spain looked into using bacteriophages as a means to transcribe antibacterial DNA into the bacterium already existent in bacteria within the human body. They used phage P22 of Salmonella. This method was originally researched prior to the mid evil ages where penicillin was developed. This could be the future of medicine.

http://www.britannica.com/EBchecked/topic/48324/bacteriophage/
https://www.landesbioscience.com/journals/mge/2013MGE0020R.pdf