Transcriptome Analysis of Sponge Response to Wounding Revealed Putative Orthologs of Cancer-Related Human Genes

 

        The wounding of sponges allows researchers to understand the fundamental processes that control how healthy tissues are maintained in response to injury. The response was remarkably similar to the way cancer works.
        This study focused on the Aplysina aerophoba transcriptomic response to wounding by grazers and mechanical injury. Their response was evaluated by analyzing the differential gene expression in RNA sequence data. According to Wu et al., “In the set of proteins codified by sponge genes responding to mechanical damage, [they] identified putative orthologs of human proteins involved in G-protein coupled signaling pathway, ubiquitination, and components of the MAP kinase signaling transduction pathway”. These genes are associated with cell adhesion, proliferation, and differentiation. When these behaviors become unregulated, it results in a tumor.
        Putative orthologs of cancer-related human genes allow researchers to assess the mechanisms of evolution through the lens of genes with the same biological function in other animal phyla. This area of study seems promising because, unlike other organisms involved with cancer research due to their regenerative capabilities, such as planarians, sponges are the first animal lineage to appear on Earth.

What To Read Next: A sponge makes a molecule called manzamine A which stops the growth of cervical cancer cells.

Spiny Mice Can Regenerate Damaged Tissue Without Subsequent Scarring

Progression of Regeneration of Skin Tissue

        In a recent study, it was found that African Spiny Mice (genus Acomys) could regenerate their kidneys after suffering damage to them. They could also regenerate their kidneys without having any dangerous or life-threatening scarring, as other animal species would.

        It has been known for quite some time that Spiny Mice could regenerate basic tissues, such as their skin, when there was damage or removal of the tissue. This regeneration happens because of the inactivity or absence of the p21 gene. The p21 gene is a cell cycle inhibitor gene, and for a long time, was considered a tumor suppressor gene. It inhibits cyclin-dependent kinase and acts to prevent protein retinoblastoma phosphorylation by the inhibition of cyclin E/cdk2 complexes that are required for Rb phosphorylation. 

        However, when scientists damaged their kidneys, simulating kidney disease in the mice, they were able to regenerate and heal their tissue completely. This shows that the p21 gene can regulate regeneration in mammals with complex tissues and organs as well.

Harvard Does it Again: Unlocking the Genetics Behind Regeneration

If there is one thing everyone knows about the folks at Harvard, it is that they are are really smart. They have managed to prove that once again, as a study conducted at Harvard University has made a key discovery to unlocking the secret of regeneration in certain animals. As most of us know, certain animals like salamanders or starfish can regenerate their leg or even entire body if necessary. The results of this Harvard study claim that there is a noncoding master control gene, called Early Growth Response (EGR) that turns key genes on and off to initiate regeneration. This study was performed on three-banded panther worms, shown below, which are capable of almost complete regeneration. The EGR flips on the switches in coding regions and stimulates a change in shape of the genome, allowing previously inaccessible genes and areas on the DNA to be turned on for regeneration. This EGR gene is necessary for regeneration to occur, as it cannot happen without this EGR turning on other necessary genes. However, just the presence of the gene alone does not lead to regenerative abilities, as human beings possess the EGR gene but, obviously, cannot regenerate our limbs. This is thought to be because EGR turns on different genes in humans and essentially serves a completely different purpose.

Although this new information cannot be applied to regeneration in humans at the moment, I still believe this is a great scientific breakthrough. I found it interesting that the key to regeneration was actually in the introns of the worm DNA, as we have always been told that the purpose of these intron sequences that do not code for anything and are not expressed is unknown. Knowing how big a role these introns play in something as complex and crucial as regeneration may lead to more discoveries regarding introns in humans and other organisms. Furthermore, while we may never be able to regenerate entire limbs, this discovery may aid us in our research on organ regeneration or the regeneration of other smaller things. This may allow us to better combat cancer and reverse organ damage and brain damage. One other really interesting fact that I took away from this research was that the genome is more of a dynamic shape than a set one, as different areas and sections of DNA can be exposed or hidden depending on the presence of EGR.

The genetics of regeneration

In a study funded in part by Harvard University researchers uncover the genetic “switches” responsible for whole body regeneration. Many animals are capable of regenerating lost limbs or even half of their bodies. Researchers look to their genetic code for answers on what genes are responsible for granting these animals this amazing ability. By studying the three-banded panther worm they have come to discover that a piece of non-coding DNA controls the activation of a “master control gene” called early growth response or EGR for short. This EGR acts as a sort of control panel switching other genes on or off. The researchers had to assemble the worm’s genome sequence in order to understand exactly what was taking place and how. They were able to decrease the activity of the EGR gene and discovered that without it, regeneration simply does not occur. Humans also possess this gene however it seems to be wired differently in us than it is in other species unfortunately for us. The researchers hope to discover whether the genes activated during regeneration are the same ones activated in development or if a whole different process is taking place on a genetic level. This discovery opens huge doors into the future of genetics. Perhaps one day we will be capable of activating regeneration in humans who have lost or deformed limbs. Instead of needing an organ transplant people could simply regenerate damaged organs. Regeneration may just be the future of medical science.

Long Lived Lonesome George Clues to Longevity

Charles Darwin developed the idea of natural selection using the tortoises he found on the Galapagos island back in 1835. He preached the idea that these amazing animals adapted there shell to help them survive the lifestyle they endured. In 2012, Lonesome George- the longest living original turtle from the islands- passed away. However he was still giving hints to scientists about longevity and good health. Dr. Aldagisa Caccone,  sequenced the entire genome of Lonesome George and then compared it to other genomes of living animals. She found that there was a gene mutation, IGF1R, that is also found in humans that could be key to longevity in the turtle AND humans.  This gene has one copy in the human genome however the tortoise carried 12. This makes it much more effeceint to carry out these processes to help the turtle live a century.

The amazing part about these tortoises is that they offer so much information to humans. If we can study them more and learn about there genome, we could have solutions to regeneration of body parts. They could survive temperatures that humans could not possible survive. And much like in 1835, were the tortoises were helping the world understand evolution, Lonesome George is once again teaching the world about adaptation and longevity.

Superpower Research

An article in the NY Times, Seeking Superpowers in the Axolotl Genome, discusses a regenerative amphibian, the Axolotl. Also known as the Mexican walking fish, this salamander has the capability of regrowing most of its body parts. While some animals are able to regenerate to some degree, these little guys are almost limitless. Jeremiah Smith, an associate professor from the University of Kentucky states, "as long as you don't cut off their heads, they can grow back a nearly perfect replica of just about any body part, including up to half of their brain". This is why researchers are working on improving maps of their DNA. These creatures can only be found in canals in the far south of Mexico City due to habitat degeneration and imported fishing. However, captive axolotl are thriving in laboratories. Unlike most amphibians, these salamanders reach sexual maturity and spend their lives as large tadpole babies. Their genome is about ten times the size of that of a human, however, a team of researchers have published in Genome Research the most complete assembly of DNA yet. Dr. Keinath and her colleagues mapped more than 100,000 pieces of DNA on chromosomes making this the largest genome to be assembled at this level. They used an approach referred to as linkage mapping, which relies on trend that DNA sequences that are physically close together on a chromosome tend to be inherited together. Using such technique, axolotls and their close relatives, tiger salamanders were crossed to track patterns of gene inheritance. The researchers were able to identify the axolotls' sequences of DNA and where they sat along the 14 chromosomes. This data is providing information for the process of human regenerative medicine.

Regeneration of the body is a fascinating and useful capability. More research into this ability would be positive because it could eventually lead to regenerative human, or other species who lack this feature, medicine. If humans were able to regenerate body parts, it could have a detrimental impact. The ability to regenerate could cut back on health care costs because transplants may be lessened, it could prolong life or improve the quality of life.

What We Can Learn from the Cockroach Genome

     The second largest genome in the world belongs to the Periplaneta americana, more commonly known as the cockroach. With a genome larger than that of the human's, there is a lot of data that can be collected from the cockroach. Within its genetic code holds the insect's  secrets to survive in the harshest environments and on such a variety of food in its diet. The cockroach's genome was actually sequenced outside of the United States. At the South China Normal University in Guangzhou, researchers found that the groups of genes related to the immune system, sensory perception, detoxification, and growth and reproduction were all enlarged. This enlargement helped to explain how the cockroach is able to survive in a variety of conditions. Such as freezing cold and blistering heat. Some cockroaches have been observed living for as long as days without their head and showed regeneration of lost limbs. 

     Researchers have taken the data collected from the cockroach genome and are attempting to apply it to humans in hopes to prolong the live span of humans. Some of the genes the researchers are 
attempting to use in humans include genes coded for safety. Nearly 300 genes in the cockroach are able to sense bitter tastes. Which assist the cockroach in which foods are safe to eat and which foods to avoid. Researchers also observed what genes were responsible in limb regeneration. I believe that this is of vital importance in the scientific community. As information in this research can be applied to the human genome. The cockroach's superb ability to survive and adapt to drastic changes in their environment could be taken and, hopefully, be put to use in the genes of humans to enhance the live and livelihood of the human race in the future.

Article Link: http://fortune.com/2018/03/27/american-cockroach-genome-roaches/

Genome of Cockroach from Chinese research: https://www.nature.com/articles/s41467-018-03281-1

The Genetics of Skeletal Muscle Development and Regeneration

Scientists at Brigham and Women’s Hospital discovered that there was reduced muscle growth and impaired regeneration in zebrafish larvae that had a mutation in DDX27. They discovered this mutation and its affects using genetic mapping. The researchers found that DDX27 is associated with protein synthesis and ribosome biogenesis in the skeletal muscles. Protein production and regulation is disrupted by the loss of DDX27, which affects the function of skeletal muscle. Skeletal muscle mass is maintained by a balance between degradation and protein synthesis, a disruption of this balance leads to a loss in skeletal mass. The loss of skeletal muscle mass is a common component of many diseases; it often leads to a reduction of muscle function, which is debilitating and can lead to death. "A major hindrance in the development of effective therapies for skeletal muscle diseases thus far has been a lack of understanding of the biological processes that promote muscle growth and repair," said Vandana Gupta. "Our study is one of the first efforts to provide specificity to the processes controlling protein synthesis in muscles, which will hopefully allow for the development of effective targeted treatments for skeletal muscle diseases." The researchers plan to do further research to look at how protein synthesis is altered in different diseases and they hope to target an approach to regulate DDX27 pathways which will allow restoration of muscle growth and regeneration.

For more information on the genetics of skeletal muscle growth and regeneration, take a look at this scientific paper by Stephen M. Roth. 

Decoding the Axolotl genome: Insights into tissue regeneration

In biology salamanders have become a model for evolutionary and developmental studies. In this study it focuses on one salamander, which is the Mexican axolotl (Ambystoma mexicanum). They choose this salamander in particular because they are known for their ability to regenerate body parts. If this salamander looses a body part, within weeks the limb will grow back with, muscles, bones, and tissue. To understand regenerate and why it is very limited in most species, scientists need to have access to genome data. In the Axolotl due to their size, there are 32 billion base pairs, which is 10x larger than the human genome.


International team of researchers have now assembled, annotated, and sequenced the complete axolotl genome, which is the largest genome to ever be decoded. They did this using the PacBio-platform, which a sequencing technology that produces long reads to span large repetitive regions. Those who analyzed the assembled genome discovered many features that seem to point uniqueness of the axolotl. It was also discovered that an essential development gene named PAX3 is completely missing from the genome and it function has been taken over by another genome named PAX7. Both of these genes play a key role in muscle and neural development.

https://www.sciencedaily.com/releases/2018/01/180124131716.htm

https://www.mpg.de/11886639/decoding-the-axolotl-genome

I Can See Clearly Now the GABA is Almost Gone! - How Zebrafish Recover From Blindness

A recent study funded by the National Eye Institute found a link between the neurotransmitter GABA, or gamma-aminobutyric acid, and recovery from blindness in zebrafish.  For some time now, scientists were aware of the zebrafish's ability to recover from loss of vision that would normally blind humans permanently.  This is due to the zebrafish having a miraculous ability to regenerate cells in the retina.  Prior studies showed that dying retinal cells produced signals to trigger Muller glia, which revert back to an undifferentiated state and divide.into new cells.  Studies in mice on the brain and pancreas indicated that GABA could play a role in the regeneration process, where low levels signaled stem cells to  divide.  The researchers of the current study, therefore, hypothesized that GABA in zebrafish could be a factor in the regeneration of retinal cells.  To test their theory they injected zebrafish with GABA inhibitors.  They found that these fish responded with retinal cell regeneration.  Fish with retinal damage that were given high levels of GABA, on the other hand, displayed little to no regeneration.  These findings clearly support the hypothesis that GABA plays a very important roll in the regeneration of new cells.

I found this article interesting because I often joke about how I'm going blind because my vision is so poor.  But on a serious note I think the findings in this study could be very significant for finding cures to diseases in humans that affect vision, and it could lead to new treatments to cure blindness.  It is also the first study to report these kind of results, so with more experiments in the future it would be fascinating to see what else researchers find out about the subject.

How fish can regenerate eye injuries at the cellular level

Fish have the special ability to regenerate injuries to the retina at a cellular level. Scientists from Heidelberg University’s Centre for Organismal Studies, or COS, have discovered as to how the regeneration process starts by studying the Medaka fish. There is one genetic factor that triggers two steps for this process to occur. The two steps are cell division and differentiation of progenitors into new and different cell types. Stem cells have been a huge topic as of late in the medical world. Stem cells can be used to correct faults in the body. However, we have not yet been able to actually figure out how to perfect this system. One-day scientists hope that we will actually be able to use stem cells to help repair various injuries. In a study, researchers looked into the retina of fish and found that they can completely repair injuries to the retinal nerve cells. There are special glia cells that act like stem cells. Both fish and humans have these cells in their eyes. These cells are also called Muller cells. Professor Wittbrodt of COS explored if these cells could be activated and what would stimulate the regeneration process. A gene called Atoh7 is responsible for cell differentiation and is triggered by a single genetic factor. There are several steps that go into the regeneration process of a fish’s eye. The glia cells first start to proliferate. “First the Müller cells near the injury start to proliferate. The resultant neuronal clusters contain the progenitor cells for the cell types of the retina. In the last step, these progenitors differentiate and turn into the neuronal retinal cells to be restored”. These cells supposedly show signs of being able to repair any injuries. The Atoh7 gene is the big factor, which fulfills two functions and triggers proliferation and differentiation into various retinal cell types. Scientists hope that one day we will be able to decode this ability in humans.

Regeneration is a very interesting and unique ability that various species possess. By studying these species more and more I believe that one day we will be able to figure out a way to possess this ability in humans. Being able to cure someone’s blindness would be a miracle. Hopefully one day it will only take one simple surgery for someone to repair their damaged retinal cells. I think more research and funding should go into fully understanding the regeneration process.

Links:

https://www.sciencedaily.com/releases/2016/05/160506100241.htm

http://www.eurostemcell.org/factsheet/regeneration-what-does-it-mean-and-how-does-it-work

Octopus Genome holds clues to uncanny intelligence

 

Octopuses possibly one of the most intelligent creature in the sea.  With their ability to shape-shift, camouflage, critically think, and analyze complicated tasks, the question remains, are Octopuses Alien?   The octopus’s genome is almost as large as a humans and contains 33,000 protein-coding genes compared to humans who only have fewer than 25,000. The octopus has 168 of the gene protocadherins which regulate the development of neurons in which 2/3 of this gene is distributed throughout the limbs of the creature.  This enables their tentacles to think on its own, even when their tentacles have been removed from their bodies. 

According to researchers they want to analyze and understand the genome of the octopus in order to give possible insight on how their cognitive skills have evolved.  By understanding this creature and its complicated genome, who know what could happen.  Maybe the octopus has genome sequence of regenerating their own limbs, and by understanding how it works, it could lead to us humans regenerating out own diseased or lost limbs