BioQuakes

AP Biology class blog for discussing current research in Biology

Author: chlorolil

The Cure Before Being Born

lab mouse – Photo credit to Wikimedia Commons

A team of researchers from the University of Pennsylvania and Children’s hospital of Philadelphia has seen exciting results in their experiment on mice fetuses with an inherited liver disease.  The team removed the amniotic sac containing the fetus from the mother’s uterus, before injecting in a vein of thee fetus near the liver with CRISPR. This was to ensure that the genetic modification would be in the liver cells and would not affect any other vital organs. The fetus was then placed back into the uterus and the mother was thankfully unaffected by the modification, allowing for all the babies to be born without any issues.

The team used a more recently invented form of CRISPR called base editing instead of the well-known  CRISPR-CAS9.  Rather than cutting and inserting a sequence of DNA, a single nitrogenous base was replaced with another.  This newer method showed significantly less “genetic havoc”, unknown consequences for a cell that has been genetically modified with CRISPR.

The disease they targeted was a tyrosinemia type I, a mutation that effects 1 in 100,000 newborns globally, which causes causes the amino acid tyrosine to be metabolized into toxic products, which build up and cause damage to liver, and can eventually destroy it.   The scientist sought to disable the HPD gene, which creates enzymes that help to break down tyrosine.  By changing a cytosine base to thymine base, the toxic products are never produced.

Tyrosinemia type I – Photo credit to Wikimedia Commons

As the mice grew and developed, the researchers were astounded to find that despite only 15% of their liver cells having been the altered with the base edit, the genetically modified mice were surviving better and gaining more weight compared to those treated with traditional methods of drugs and monitored diet.

This is definitely a step in the right direction to eliminating genetic diseases, but base editing, especially for diseases due to multiple mutations might be more difficult, as many bases would need to be edited.  What do you think: more safe, yet possibly difficult base editing method or cut-insert method?

Message Intercepted – Commence attack on bacteria!

Tevenphage – Photo credit to Wikimedia Commons

While experimenting, a group of scientists noticed that a A virus, VP882, was able to intercept and read the chemical messages between the bacteria to determine when was the best time to strike. Cholera bacteria communicate through molecular signals, a phenomenon known as quorum sensing, to check their population number.  The signal in question is called DPO.  VP 882, a subcategory of bacteria’s natural predator, the bacteriophage, waits for the bacteria to multiply and is able to check for the DPO.  Once there is enough bacteria, in the experiment’s case they observed cholera, the virus multiples and consumes the bacteria like an all-you-can-eat buffet. The scientists tested this by introducing DPO to a mixture of the virus and bacteria not producing DPO and found that that the bacteria was in fact being killed.

The great part about VP 882 is it’s shared characteristic with a plasmid, a ring of DNA that floats around the cell. This makes it easier to possibly genetically engineer the virus so that it will consume other types of bacteria. This entails it can be genetically altered to defeat other harmful bacterial infections, such as salmonella.

Ti plasmid – Photo credit to Wikimedia Commons

Current phage therapy is flawed because phages can only target a single type of bacteria, but infections can contain several types of different bacteria.  Patients then need a “cocktail” with a variety of phages, which is a difficult due to the amount of needed testing in order to get approved for usage.  With the engineering capability of using a single type of bacteria killer and the ability to turn it to kill bacteria, phage therapy might be able to advance leaps and bounds.

As humans’ storage of effective antibiotics depletes, time is ticking to find new ways to fight bacterial infections.  Are bacteriophages and bacteria-killing viruses like VP 882, the answers?

Genetic Engineering on Gut Bacteria!?

E. coli on MAC – Photo credit to VeeDunn on flickr under Creative Commons License

Researchers at the Wyss Institute at Harvard University has successfully tested a genetically engineered signaling bacteria within a mouse’s gut. Having known that the many types of bacteria in the human gut can communicate through “quorum sensing” , researchers set to observe a particular type of quorum sensing, acyl-homoserine lactone sensing, which has not been observed in the mammalian gut. They wanted to test if using that particular type of signaling could create a genetically engineered bacterial information transfer system.

Using a strain of E. coli bacteria, they created two different colonies, each with a different genetic change: one was the “signaler”, it contained a copy of the luxl gene which produces a quorum-sensing molecule when activated, and the other was the “responder”, which contained a “cro” gene turning on a “memory element” in the responder.  This “memory element” expressed another copy the the pro gene, which allowed for the loop to continue, and the LacZ gene, which made the bacteria turn blue!

LacZ gene expression – Photo credit to Viraltonic on Wikimedia Commons under Creative Commons License

The researchers analyzed fecal samples of mice given signaler and responder E.coli and they were happy to see the signal transmission, blue coloring, was evident in the samples. This result meant that they had created a functional communication bacteria system in the mouse’s gut.

The researchers then repeated their experiment with a different type of bacteria, S. Typhimurium, as the “signaler” and E. coli as the “responder”, and they were pleased to see similar successful results.  They were able to successfully confirm that is possible to genetically engineer these communication circuits between different species of bacteria in the mammalian gut microbiome.

These tests are merely stepping stones for the bigger goal of creating genetically modified bacteria that will help humans in various different ways: detecting and or curing diseases, improving digestion, and so on. Isn’t it cool that something we barely realize is inside us has such a developed communication system that we might soon be able to cultivate more benefits from? What do you think would be some other benefits to be being able to genetically modify our gut microbiomes?

 

 

Fighting the mosquito disease problems with… mosquitos?

Since the discovery of CRISPR-Cas9 system (Clustered Regularly Interspaced Short Palindromic Repeats), gene editing has become a highly debated topic. One of the reasons backing the use of CRISPR-cas9 is to prevent diseases. These diseases include mosquito-borne diseases such as zika, dengue fever, and malaria.  Malaria in particular kills around 3,000 children every year. Various groups of scientists have worked on genetically modifying mosquitos to stop the spread of malaria by making female offspring sterile and unable to bite, making male offspring sterile, or making mosquitos resistant to carrying diseases. A point of concern was if the modified gene would stay relative and would carry from generations. In order to make offspring, genes from both parents must be used, resulting in the offspring carrying the modified gene only half the time.  In particular cases, mutations would occur in the altered DNA, which nullified the genetic changes.  This has been solved by developing a gene drive, which makes the desired gene dominant and occur in the offspring almost 100% of time.  This entails almost the entire mosquito population could have this modified gene in as little as 11 generations.

Image by Author

Recently, the government of Burkina Faso, a small land-locked nation in west Africa, has approved for scientists to release mosquitos that are genetically modified anytime this year or next year.  The particular group of mosquitos to be released first is a group of sterile males, which would die rather quickly.  Scientists want to test the impact of releasing a genetically modified eukaryotic organism in the Africa. It is the first step in “Target Malaria” project to rid the region of malaria once and for all.

 

One of the major challenges in gaining allowance to release the genetically modified species was the approval of the residences, who lack words in the local language to describe genetics or gene editing.  Lea Pare, who leads a team of scientists modifying mosquitos, is working with linguists to answer questions the locals may have and tp help develop vocabulary to describe this complex scientific process.

What do you think about gene editing to possibly save millions?

Read the original article here.

View a video explaining how scientists can use genetic engineering to fight disease here.

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