Molecular Biology – BioQuakes

On October 7, 2019, three scientists- William G. Kaelin, Gregg L. Semenza, and Peter J. Ratcliffe- won the 2019 Nobel Peace Prize in Physiology or Medicine for their groundbreaking discovery in the 1990’s of how cells detect and respond to the presence of oxygen. That may not seem very significant-even Ratcliffe’s colleague’s dimissed his facination with how organs respond to oxygen availability-but the applications are profound. In fact, the Nobel prize was not awarded until recently for this very reason: to evaluate the “when the full impact of the discovery has become evident” (Ralf Pettersson, a former Nobel Selection comittee chairman). Well, their research has provided an possible explaination for the rapid metastasis for which cancer cells are notorious.

An image released by the National Cancer Institute, part of the National Institute of Health, that depicts malignant breast cancer cells (brown stained) metastasizing within the liver.

According to Ratcliffe’s research, cells produce a complex of proteins called the hypoxia-inducible factor, HIF, that help increase the level of oxygen when cells are oxygen deficient. The HIF turns on genes necessary for the production of the hormone erythropoietin, EPO. In turn, the EPO protein hormone signals for red blood cells to be produced in the bone marrow. Through oxygen-carrying hemoglobin, the red blood cells carry more oxygen to tissues and cells. For example, when the body undergoes hypoxia in response to lack of oxygen, like when people occupy high altitudes, HIF turns on production of EPO.

However, when the oxygen levels are sufficient in the cell, proteins called ubiquitin will bind to the HIF and induce it’s destruction. In this way, cells sense when oxygen levels are low or high and can respond accordingly by regulating the presence of HIF.

That’s pretty cool right? It gets better.

Through the individual work of Semenza and Kaelin, cancer cells were discovered to sense oxygen levels by manipulating VHL. While conducting their separate research, both Semenza and Kaelin hypothesized that cancer cells were searching for oxygen when they spread. Kaelin, as a cancer biologist, took specific interest in von Hippel-Lindau disease, a rare hereditary disease in which either malign or benign tumors form in mostly in the nervous system, pancreas, adrenal glands, and kidneys. The VHL protein, which the VHL gene codes for, in humans helps prevents tumor formation by recognition of the indicator hydroxyl groups placed on HIF by enzymes when the oxygen level are normal. In this case, VHL knows to destroy HIF. On the other hand, if the oxygen levels are low, the HIF lack the hydroxyl groups and are ignored by VHL. During research, he discovered that in these type of cancers, the VHL genes are mutated so that VHL becomes inactive. As a result, it can no longer regulate the quantity of HIF proteins thus, the HIF level increases. Increased HIF levels mean more oxygen for cancer cell, which multiply rapidly because of their now readily available supply of oxygen. This knowledge is vital since Harvard cell biologist Andrew Murray say that “tumors can grow to only about 1 millimeter across without making new blood vessels, because oxygen can diffuse only about half a millimeter away from a capillary before cells consume it”.

The trio’s research is fascinating to me, because this knowledge could be revolutionary in preventing the development and spread of cancer cells. What other biological issue do you think that the discovery of oxygen sensing could solve?

Crispr-Cas9 is the gateway to a new frontier in genetic engineering. Here’s The good and the bad.

By chromison

On March 13, 2018

In Student Post

For a number of years now, molecular biologists have been diving increasingly further into the field of genome editing. The latest development into the field is the emergence of CRISPR-Cas9. CRISPR-Cas9 has risen to prominence over other potential methods of genome editing due to its relatively simple construction and low cost. CRISPR-Cas9’s original primary and intended purpose was to help fix mutations within DNA, and with this it could theoretically help eradicate entire diseases. This application of CRISPR is wholly positive, however with the increasing prevalence of the technique other potential uses have been discovered, and some of these potential uses raise profound ethical questions.

One of the main concerns of people skeptical about CRISPR is their assertion that once the door to the wholesale genetic editing of offspring is open, there is no going back. This, on its own, is a reasonable concern. The ability to choose a child’s sex, eye color, hair color and skin complexion is very likely to be made available to by CRISPR in the coming years. CRISPR does not yet have the capability to influence more abstract elements of the genome, such as intelligence and athletic ability, but this may not be far off. There are legitimate concerns that this is a slippery slope towards a dystopian society similar to the one seen in the movie Gattaca, where society is stratified into two distinct classes: those who are genetically engineered and those who are not.

Another concern raised by some scientists is the overall safety of genetic editing. A potentially very hazardous negative result of CRISPR is the possibility of an “off target mutation.” An off target mutation is the result of CRISPR mutating something other than the intended part of the genome and it could have disastrous consequences. Now, many scientists believe that with further advancements in the field the likelihood of something like an off target mutation occurring could be reduced to almost zero. However, it is important to examine the risks of any new process, and the prospect of something like an off target mutation occurring is certainly noteworthy.

For more information click here.

New technique will identify maternal and paternal contributions to specific DNA

By biolabski

On November 18, 2013

In Student Post

Photo by: gobucks2 Link: http://www.flickr.com/photos/ohiostate/4851592434/

Intro:A recent Ludwig Cancer Research study, conducted at the University of California, San Diego, School of Medicine, was published in Nature Biotechnology. It concerns a new technique, called HaploSeq, that can determine (1) whether a specific gene sequence is maternal or paternal (2) how to better match organ donors (3) how to better understand human migration patterns. This will aid studies concerning how genes contribute to diseases and will be revolutionary in its contributions to modern medicine.

Old Technique: Current gene sequencing is considered quick and cheap: it takes one week and costs $5,000. But, except for sex chromosomes, everyone has two copies of each chromosome, one from the dad and one from the mom. These techniques cannot distinguish between the two, so the source of a gene cannot be determined.

New Technique:

Disease: It distinguishes which genetic variants occur together, concluding that they came from one parent due to their juxtaposition. People at risk for cancer usually have many DNA mutations. This technique can permit scientists to determine if mutations are on same or different chromosomes, assessing level of the risk. Risk is reduced if two mutations are on one chromosome, for the other chromosome can make up for the mutated one.

Organ Donors: A variety of genes contribute to compatibility, but there is variability among them. This technique can determine if DNA differences can create a good match. Researchers believe that in the future, a DNA database can be created to better pair donor and recipients.

Human Migration Patterns: This technique will facilitate the analysis of human migration patterns and ancestry. People can simply compare their DNA to that of others to find any common ancestors. This will allow scientists to compare individuals and their relationships to others on a microscopic level. This contributes to the HapMap project, an international project to access worldwide human genetic variation in order to combat diseases.

Significance: Bing Ren, a scientist conducting this study, said: “In the not too distant future, everyone’s genome will be sequenced. That will become the standard of care.” DNA sequencing is the next step in revolutionary medical techniques, making this study a revelation.

BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: Molecular Biology

The Oxygen Sensing Discovery: A Huge Impact on Cancer Research

Crispr-Cas9 is the gateway to a new frontier in genetic engineering. Here’s The good and the bad.

New technique will identify maternal and paternal contributions to specific DNA

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