AP Biology class blog for discussing current research in Biology

Author: eukericotic

Could Christmas Island rats make a comeback? Thanks to CRISPR gene editing, they might!

From climate change to overhunting by humans, there are many factors which contribute to the extinction of species in the animal kingdom. The Christmas Island rat, also known as Maclear’s rat, went extinct a century ago in what is believed to be the first and only case of extinction of a species due to disease. It has always been believed that once a species goes extinct, it is gone for good. That is until recently when scientists began experimenting with “de-extinction” efforts to bring back the Christmas Island rat.

As published March 9 in the science journal, Current Biologya team of paleo geneticists from the University of Copenhagen recently conducted a study into gene sequencing the Christmas Island rat, in order to estimate the possibilities of future gene editing experiments which could bring the species “back to life”. The process of genetic editing for de-extinction efforts, as explained by the research team in their abstract, consists of first identifying the genome of the species and then editing the genes of similar species to make it more similar to that of that extinct one. The team used frozen somatic cells of the extinct rats, cells with a 2n number of chromosomes which are made during the process of mitosis. The team was able to sequence the rats’ genome, aside from some small portions which remain missing. They then had to identify the modern species which they could gene edit. Their findings established that the Christmas Island rat shares around 95% of DNA with the modern Norway brown rat. At this point, it

Now that the rat’s genome has been sequenced to the best of the team’s ability and a similar species has been identified, the gene editing possibilities are endless, especially with CRISPR technologies and techniques. “CRISPR” stands for Clustered Regularly Interspaced Short Palindromic Repeats in DNA sequencing. This system was discovered by a group of scientists, led by Dr. Emmanuelle Charpentier. CRISPR uses Cas9, an enzyme which cuts DNA at specified sections as guided by RNA. There are three different types of edits drone with CRISPR technology: disruption, deletion, or correction/insertion. Disruption editing is when the DNA is cut at one point and base pairs are either added or removed to inactivate a gene. Deletion editing is when the DNA is cut at two points and a larger sequence of pairs is removed. Correction/insertion editing is when a new gene is added into a sequence using homology directed repair.

Thomas Gilbert, the lead scientist on the team, says that he would like to conduct CRISPR gene editing experiments on living species of rats before attempting to replicate the DNA of an extinct species. For example, attempting to mutate the DNA of the Norway brown rat into that of the common black rat. Once this experiment is conducted, the possibilities of reviving the Christmas Island rat will be more clear. Until then, we can only hope! Do you think it’s possible to see the Christmas Island rat revived anytime soon?

How Fruit Flies Changed Humans’ Understanding of ADHD and Autism

Think about driving on the highway. There may be music blaring on the radio, a friend chatting away in the passengers’ seat, birds flying over head, and hundreds of shiny multicolored cars whizzing by. Still, you focus on the road ahead of you and all the levers you must pull and pedals you must press to complete your drive. Your brain’s ability to focus solely on the task at hand is what scientists refer to as the phenomenon of habituation. Habituation is a when an organism is introduced to stimulus like a sight or sound so many times that the brain can begin to filter it out and no longer respond to it as strongly or at all. This concept of habituation has been known to scientists for years, but poorly understood until now. A study conducted and published recently in the journal, PLOS Genetics, by scientists at the CSIR-Centre for Cellular and Molecular Biology in Hyderabad, India, may finally explain this phenomenon.

Led by scientist and scholar Runa Hamid, the team utilized fruit flies to study how these tiny organisms could learn to tune out specific scents and only focus on the ones they wanted and needed. Fruit flies, also known by their scientific name of Drosophila, are commonly used in scientific experiments as their DNA is shockingly similar to that of humans. For their tests, the team exposed wildtype larvae to certain chemical odors like Ethyl acetate. At first exposure, the flies flocked to this odor. After just 5 minutes, the flies began to avoid this odor and search for other sources of food! However, some flies took longer to become habituated than the rest and some became hypersensitive instead, seemingly being more fixated on the odor the more that they were exposed to it.

The researchers then tested the brain activity of the flies. They found that flies that took longer to tune out the scents and/or became even more sensitive to them had fewer choline transporters in their brains. Produced in the liver, choline is an essential nutrient which helps compose Acetylcholine, a neurotransmitter which binds as a ligand to the receptor protein to Acetylcholine receptor pathways. As we learned in AP Bio, neurons in the brain release neurotransmitters to diffuse across a “synapse”, the small gap between the signaling cell and the target cell. In this specific case, the Acetylcholine binds to the receptor protein site embedded in the membrane of brain cells and opens the ligand-gated ion channel. However, to make these neurotransmitters, the neurons need transport proteins to bring nutrients like choline into the cell. Without choline, neurons cannot produce Acetylcholine and the cell signaling pathways which Acetylcholine stimulates will not be signaled, or yield a response.

In short, flies with a sufficient amount of choline receptors in the brain produced the neurotransmitters needed to signal the Acetylcholine receptor pathway; These flies were able to quickly adapt to the stimulus provided. The flies that struggled to focus and tune out the scent were proven to have fewer choline receptors, meaning their brains did not produce adequate amounts of Acetylcholine. This helped the scientists conclude that Acetylcholine, specifically the molecules that allow for its thorough production, are necessary components of the phenomenon of habituation.

As the behaviors of poor focus and/or hypersensitivity to stimuli are traits of ADHD and Autism Spectrum Disorders in humans, the scientists believe there is a link between the biochemistry of the fruit flies and humans with these disorders; They concluded that reduced choline transport proteins in the brain of humans are a likely cause of the attention related symptoms of ADHD and Autism. Although further studies will need to be conducted, the high levels of shared DNA in humans and fruits flies mean that our biochemistry is likely wired in similar mechanisms to that of the flies. Thanks to the work of these scientists to understand one poorly understood biological phenomenon, they have opened the door into further research and understanding of another.

How Mice and Mental Health Led to This COVID-19 Treatment Breakthrough

Ever since the initial outbreak of COVID-19, scientists have worked tirelessly to innovate and find the antidote to the virus which has infected millions and tragically killed hundreds of thousands. Such unprecedented times have led researchers to reconsider everything they already know and take intellectual risks.

One innovator whose experimental hypothesis may save many is Angela Reiersen, a child psychiatrist from Washington University School of Medicine in St. Louis. When she fell ill with COVID-19 in March 2020, Reiersen thought back to a study she had read about the effects of the lack of the sigma-1 receptor in mice and how the lack of this receptor protein led to massive inflammation and overproduction of cytokines. Cytokines are a part of the inflammatory response that occurs when pathogens sneak past the barrier defenses of the innate immune system and permeate cells. Upon entry of a pathogen, mast cells secrete histamines and macrophages secrete these cytokines. These cytokines attract neutrophils which then digest and kill the pathogens and other cell debris. Although cytokines are crucial to a functioning immune system, overproduction of cytokines can be extremely dangerous as it can lead to septic shock, in which the immune system becomes extremely overactive. This has become the cause of death for many COVID-19 patients.

As a psychiatrist, Reiersen worked regularly with SSRIS, or selective serotonin uptake inhibitors, in the treatment of conditions like depression and obsessive compulsive disorder. SSRIs help the human brain by increasing the level of serotonin available between nerve cells, but they also activate the S1R in the Endoplasmic Reticulum. Reiersen wondered, if the lack of the S1R causes fatal levels of inflammation, can we prevent extreme inflammation from COVID-19 through the use of SSRIs?

There have been multiple studies performed to test this line of reasoning, both including and independent of Reiersen. The most notable study was performed as part of TOGETHER, an international organization seeking to test possible unorthodox treatments for COVID-19. The trial was a collaboration between researchers from McMaster University of Canada and Cardresearch, a research clinic located in Brazil. The team in Brazil located 1,497 unvaccinated adults who were deemed “high risk” for COVID complications in their first week of showing symptoms of COVID. Conducted at 11 different research sites in Brazil from January to August, the study provided participants with a 10 days supply of either 100 milligrams of fluvoxamine, an SSRI, or a placebo pill. The researchers monitored the participants for 28 days after, as well.

In the end, 15.7% of participants who were given a placebo pill ended up having major complications from COVID-19, compared to 10.1% of participants who were given fluvoxamine. The gap may seem slight, but this is because not all patients took their full dosage due to gastrointestinal complaints. However, out of patients who completed their course of medication, 66% were safe from any complications and the mortality rate was cut by 91%!

Thanks to the research of Reiersen and many others, fluvoxamine is now considered a solid treatment plan for COVID-19 infections, especially in high risk individuals. As COVID-19 continues to infect millions around the world, who knows what new scientific breakthroughs will be made?

Sea Otters: Tiny and Toasty

Weighing in at anywhere from 30 to just under 100 lbs, sea otters are the smallest ocean mammal. Scientists have long wondered how such small animals can withstand the cold waters in which they live. Unlike other sea mammals like whales who can have hundreds of pounds of blubber to insulate themselves, sea otters have rather trim, muscular builds. Although their fur is the densest out of any creature on the planet, scientists have concluded that their fur alone is not enough to insulate their bodies from harsh coastal climates. Scientists were puzzled for years as to how these petite mammals could endure water temperatures approaching and below 0 degrees Celsius. Finally, in the summer of 2021, a group of scientists revealed they found the answer to how sea otters stay warm: mitochondrial leaking.

On July 9 2021, Traver Wright and his colleagues at Texas A&M University published their research that solved the long standing mystery of sea otter survival. For their research, the team took muscular tissue samples from 21 different otters, varying in age and habitat. The team chose to study muscle tissue as this is predominantly where metabolic reactions occur in mammals. Utilizing a tool called a respirator, the researchers measured the oxygen flow and respiratory capacity of the otters’ cells as an indicator for the amount of heat their cells are producing.

The mitochondria is an organelle found in all living cells. Often cited as “the powerhouse of the cell”, the mitochondria is responsible for many important processes within a cell, most notably the generation of ATP through the process known as the Krebs Cycle. The mitochondria also has a special process of generating heat. Peter Mitchell’s 1961 chemiosmotic theory explains how electrons being passed through the mitochondrial electron transport chain creates a proton gradient, or gradual change in concentration within an area, that drives the production of ATP. Sometimes, the protons escape the mitochondria’s inner membrane, leading to energy being released as heat. This process is called “non-shivering thermogenesis” and it is precisely what happens in the muscles of sea otters.

Because a lot of energy is lost in this process of generating heat, sea otters have a high metabolism and need to consume a lot of food to maintain homeostasis. This explains the studies of oxygen flow in and out of the otters’ muscles! The research shows that over 40 percent of the cell respiratory capacity is due to these proton leaks, showing the major significance of this phenomenon on the metabolisms of otters and how hard their bodies work to keep them warm.

The scientists’ next steps are to find whether otters are born with such traits or if they develop them when they live in cold water as a means to survive. While baby otters don’t generate heat well due to their low muscle mass, the study showed that proton leak was still heavily occurring in the babies’ cells. While the Texas A&M team made significant contributions to our scientific understanding of otters, they have also opened the door to a many new research opportunities to further our understanding and answer the new questions that their research posed.

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