BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: oxygen

We Could Be One Step Closer to Finding Life on Other Planets

I’ve always been so curious about life beyond Earth. Scientists recently discovered that there are as many as 24 planets outside of our solar system more suitable for life than Earth. They found that these planets surpass Earth in several categories, including age, warmth, wetness, and size. These factors qualify the planets to be “superhabitable” and to have optimal potential for complex extraterrestrial life. 

When searching for a habitable planet, one of the most important factors to take into consideration is temperature, which goes hand-in-hand with distance from their star. Scientists have discovered several planets at extreme temperatures, including planet KELT-9b, which is so hot that its atmosphere is constantly melting or GJ 433 d, whose discoverers described it as “the coldest Neptune-like planet ever discovered”. While both of these planets are on opposite sides of the inhospitable spectrum, there are several other planets within their star’s “habitable zone”, which are not too hot or too cold for life as we know it to flourish. 

Scientists have discovered over 4000 exoplanets, or planets outside our solar system so far. The main qualities researchers aim to identify in exoplanets in order to classify them as “superhabitable” include a nearby star of the right star and life span, as it took 3.5 billion years for complex life to form on Earth, and size of the planet. A larger size means more surface area for habitats, higher gravity, and a thicker atmosphere, which is beneficial for flight based organisms. Planets with these qualities in addition to being slightly warmer and wetter would be even more habitable than Earth. A larger or closer moon than Earth’s would also be considered “better”, because of benefits such as helping to stabilize its orbit and preventing life-disrupting wobbles. Taking all of these factors into consideration, the researchers came up with a list of the most ideal parameters for the perfect superhabitable planet. This planet “would be in orbit around a K dwarf star, which is a relatively small star star that’s slightly cooler than our sun […]; about 5 billion to 8 billion years old; about 10% larger than Earth; about 9 F  warmer than Earth, on average; moist with an atmosphere that is 25% to 30% oxygen, with scattered land and water. [It] would also have plate tectonics or a similar geological process in order to recycle minerals and nutrients through the crust and to create diverse habitats and topography, and would have a moon between 1% and 10% of its size orbiting it at a moderate distance” (livescience.com) As we know from biology, an oxygen rich atmosphere is essential as oxygen is one of the most important building blocks of life. Our cells need oxygen to produce various proteins which in turn produce more cells. Oxygen is also vital in many of our body systems and needed for the creation of carbohydrates, nucleic acids, and lipids. Other animals and plants also require large amounts of oxygen to survive. 

Out of the 24 Kepler Objects of Interest, which are unconfirmed indications of  transiting planets, spotted by the Kepler telescope, two have been confirmed as exoplanets, (Kepler 1126 b and Kepler-69c), nine are orbiting around the proper type of star, 16 are within the correct age range, and five fall into the right temperature range. KOI 5715.01 was the only candidate of the 24 that fell into the correct range for each of the three categories, but the planet’s true surface temperature is unable to be determined right now because it depends on the strength of the greenhouse effect in its atmosphere. Additionally, as all of these planets are more than 100 light-years away, many of them can’t be studied properly due to lack of technology.

I personally believe that we are on the brink of making seriously ground-breaking discoveries regarding extraterrestrial life. Technology is advancing every year, and in turn we make more discoveries each year about the enigma of space. Hopefully soon we will find out if some of these planets really do have life inhabiting them.

And The Nobel Prize in Medicine Goes To…

On October 7th, it was announced that the Nobel Prize in Medicine would be awarded jointly to scientists William G. Kaelin Jr., Sir Peter J. Ratcliffe and Gregg L. Semenza for their contributions in the discovery of how cells detect and react to the levels of oxygen in their environments. Each contributor will be receiving 1/3 of the prize share for their work in this topic.

The “Textbook Discovery”

Before we are able to understand the gravity of the discovery being awarded one of the world’s most prestigious scientific prizes, let’s set up some essential vocabulary we will need to break this concept down. Firstly, HIF-1α is the main protein that has been found to be essential to the identification of Oxygen. We have known that there exists an EPO gene which encodes for a steroid known to increase levels of Oxygen but the discovery of the HIF-1α protein is what is so astounding. What this protein does is regulate the activity of the EPO gene. Another factor which plays a large role in this discovery is the VHL gene, a gene known to be responsible for preventing occurrences of cancer. It was discovered that VHL had a link to the regulation of oxygen when low levels of the gene were linked to low level of oxygen (hypoxia). However, as more VHL was reintroduced, oxygen

levels were restored to normal.

How do HIF-1α proteins, VHL genes and EPO genes come together to create an understanding for how cells react to oxygen variation? Well, for HIF-1α to degrade, a peptide known as ubiquitin must link onto the HIF-1α and begin proteasomal degradation. It just so happens to be that VHL codes for a complex which tags proteins with ubiquitin allowing them to degrade. Finally, it was discovered that Oxygen was what binded theses two together, moving ubiquitin from the VHL over to the HIF-1α protein, thus degrading it. In other words, the more oxygen there is present, the more HIF-1α which gets degraded. Finally, the mechanism by which oxygen levels are controlled has been uncovered.

The Men Behind The Discovery

Over the span of 2 decades of research, three scientists were able to form an understanding on how our bodies respond to one of the most essential molecules in biology.

William G. Kaelin Jr. is a professor of medicine at at Dana-Farber Cancer Institute and Brigham & Women’s Hospital Harvard Medical School. As a cancer researcher, Kaelin’s main contribution was in the creation of a full understanding of the VHL disease which allowed for the link between VHL and HIF-1α to be formed.

Sir Peter J. Ratcliffe is the director of clinical research at the Francis Crick Institute in London. Ratcliffe and his team’s main contribution was establishing the connection between VHL and HIF-1α.

Gregg L. Semenza is a professor in genetic medicine at John Hopkins. His work focused on the EPO gene and how it controlled oxygen levels. He found out how oxygen is regulated, leaving only the cause a mystery.

For even more information on the scientists responsible, look into this New York Times article about them.

Nobel Prize awarded to Researchers for Key Discoveries in Cellular Respiration

Recent findings about the change in oxygen levels in cells show new important factors about oxygen that translate to one’s well-being. William G. Kaelin Jr., Sir Peter J. Ratcliffe and Gregg L. Semenza discovered how cells can “sense and adapt to changing oxygen availability,” and are now being awarded the Nobel Prize in Physiology or Medicine. Oxygen is a crucial aspect to how a cell’s functionality. Mitochondria in cells use oxygen to aid in converting food into ATP (energy), a process known as cellular respiration.

A representation of the reaction of cell respiration.

 

Gregg Semenza wanted to further look into the rise of levels of the hormone erythroprotein (EPO), a response to low levels of oxygen, or hypoxia. He found that “oxygen sensing mechanisms were present in virtually all tissues, not only in the kidney cells where EPO is normally produced.” While Semenza analyzing cultured liver cells, Semenza found a protein complex that was unknown to science. He named unidentified DNA segment the “hypoxia-inducible factor (HIF).”

Over the course of 24 years, Semanza continued to explore aspects of HIF and found two different DNA-binding proteins, now named “HIF-1a and ARNT.” Researchers worked with Semanza in finding out which parts of the HIF assist in cellular respiration. While Semenza and Ratcliffe were researching regulation of EPO, Kaelin Jr. was researching von-Hippel-Lindau’s disease (VHL). Kaelin Jr.’s research showed that VHL gene “encodes a protein that prevents the onset of cancer,” and that cancer cells lacking a functional VHL gene have “abnormally high levels of hypoxia-related genes.” But when the VHL gene was reintroduced into cancer cells, “normal levels were restored.” Eventually, Kaelin Jr. and his team found that VHL needs HIF-1a for degradation at normal oxygen levels.

Kaelin Jr. and Ratcliffe both published articles that center around protein modification called prolyl hydroxylation which “allows VHL to recognize and bind to HIF-1α degradation with the help of oxygen-sensitive enzymes.” The papers also wrote that the gene activating function of HIF-1α “was regulated by oxygen-dependent hydroxylation.” The researchers now had a much clearer idea of the effects of how oxygen is sensed within cells.

These groundbreaking finds give the science world more information about how oxygen levels are regulated in cells in physiological processes. Sensing oxygen levels is important for muscles during physical exercise, as well as the generation of blood cells and strength of one’s immune system.

The Oxygen Sensing Discovery: A Huge Impact on Cancer Research

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.

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?

 

 

Enzyme Protects Against Dangers of Oxygen

Yes, you read the title correctly: Oxygen can be dangerous.

As you may (or may not) remember, Oxygen is needed for two parts of cellular respiration. 1) For the Pyruvate made in Glycolysis to enter the mitochondria for the Krebs Cycle 2) As the final electron acceptor in the electron transport chain during Chemiosmosis. If there isn’t enough oxygen around (say, you’re running and there’s not enough oxygen to go to your muscle cells), the pyruvate made in glycolysis will not enter the mitochondria, but will instead undergo fermentation, which basically turns the NADH back into NAD+ so cycle of cellular respiration can continue.

Oxygen becomes dangerous when unhealthy cells fail to undergo cellular respiration, despite plentiful oxygen and instead undergo fermentation. This leads to uncontrollable cell growth: cancer. Luckily, scientists just discovered the enzyme superoxide dimutase, or SOD1 for short, regulates cell energy and metabolism by  transmitting signals from oxygen to glucose to repress respiration. This happens through cell signaling, when SOD1 protects the enzyme Kinase-1 gamma, of CK1Y, an important key from switching from respiration to fermentation. The results of this study were published in the Journal “Cell” on January 17th.

 

 

This diagram shows how enzymes, like SOD1, work. The substrate binds to the active site of the enzyme and the enzyme either breaks the substrate in two or puts two substrates together.

 

The interesting thing about this study is that SOD1 is not a new discovery. Scientists have known about SOD1 since 1969, but they thought it only protected against free radicals. Researcher Valeria C. Culotta calls SOD cells “superheroes” because of their many powers: protecting against free radicles and regulating cellular respiration.

According to Vernon Anderson, PhD, the result of this study might find out why cells turn to fermentation, casing cancer and some other diseases.

 

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