BioQuakes

AP Biology class blog for discussing current research in Biology

Author: isatonic

CRISPR May Be the Cure!

There are still many disorders and diseases in this world that cannot be cured, and Huntington’s disease (HD) is one of them.

HD is a neurological disorder that causes individuals to lose control of movement, coordination, and cognitive function. HD occurs because of a mutation in the Huntingtin (HTT) gene where a specific codon sequence repeats, creating a long, repetitive sequence that turns into a toxic, expanded protein clump. These clumps form in a part of the brain that regulates movement called the striatum and prevent the neurons in the striatum from functioning properly. As of now, HD still has no cure, but CRISPR gene editing (Clustered Regularly Interspaced Short Palindromic Repeats) might just be the solution.

Dr. Gene Yeo of UC San Diego School of Medicine, along with his team and colleagues from UC Irvine and Johns Hopkins University, researched RNA-targeting CRISPR/Cas13d technology as a way to possibly eliminate HD and its negative effects on the brain. CRISPR gene editing, as its name suggests, enables scientists to “edit” – add, remove, or alter – existing genetic material. The group desired to see if RNA-targeting CRISPR would be able to prevent the creation of the protein clumps that damage the function of the striatum. As we learned in AP Biology, the addition, removal, or substitution of a base of a codon can drastically change the structure and function of a protein. Each codon codes for a specific amino acid, and if multiple codons have changed due to a mutation, it is likely that the protein will fold differently than it is supposed to and will lose its function.

Yeo and his team desired to develop an effective therapy for HD, hoping to stop the formation of toxic protein clumps and alter the course of the disease. However, they did not want to create permanent changes in the human genome as a precaution. The team instead engineered a therapy that alters the RNA that turns into the protein clumps.  They conducted testing on mice and found that RNA-targeting CRISPR therapy reduced toxic protein levels in a mouse with HD, improving motor coordination. In connection with the molecular genetics unit in AP Biology, since the RNA that causes HD is altered, the protein that is translated will change since different amino acids correspond to different codons.

Transcription and Translation

Further testing will be necessary to confirm the benefits of this therapeutic strategy, but CRISPR does look like a promising medical treatment for HD and many other diseases in the future.

This Immune Cell Might Be the Key to Getting Rid of Your Allergies

There is still so much to discover about the human body. Since we are made up of 100 trillion cells, we are constantly learning more and more each day about our cells, their functions, and the processes that they contribute to.

One such cell, known as an innate lymphoid cell, was discovered about a decade ago, but all we knew was that it functions similarly to T-cells. As we learned in AP Biology, helper T-cells cells play a large role in our adaptive immune system response, releasing cytokines, which activate more helper T-cells, cytotoxic T-cells, and B-cells to fight invading pathogens and infected cells. Innate lymphoid cells are also able to release cytokines but are a part of the innate immune system, hence why they are known as the innate counterparts of T-cells. Because of their overlapping functions, many scientists believed their function to be redundant and unnecessary… until now!

ILC Cell 3

Research from the Emmy Noether Independent Junior Research Group led by Dr. Christoph Klose in Charité has shown that group 2 innate lymphoid cells (ILC2s) are a vital part of the immune response. By using an animal model and single-cell sequencing, the scientists were able to determine the main functions of ILC2s. The team found that the presence of ILC2s relates to the development of eosinophils, disease-fighting white blood cells, which help promote the immune response of inflammation. Without ILC2 present, eosinophils were not fully developed and were unable to get involved in the inflammatory processes in the tissue. The scientists also discovered that ILC2s promote epithelial cells to produce mucus and expel parasites from the body. Without ILC2s, it became increasingly difficult to produce mucus in the tissue and to combat parasites. With this study, ILC2s have finally been recognized for their own roles in the immune response!

Dr. Klose took this study one step further by examining the relationship between ILC2s and symptoms of allergies. As inflammation and increased mucus production are common symptoms of allergies and ILC2s are linked to both, it is understandable the results demonstrated symptoms of allergies were improved when ILC2s were not present. Dr. Klose hopes to conduct further research on these cells and believes they may be the key to developing new allergy therapies. It is incredible to see how gaining a better understanding of one of our cells can unlock a door to new treatments, medications, and advancements in the field of medicine.

 

 

 

The APOE Gene: little known secret to COVID-19 survival

I’m sure you all have heard it before – surviving COVID-19 is based on your age, sex, and pre-existing health problems – but what if I told you that another factor you should consider is your APOE gene.

A 22K fragment of APOE4 (APOE4) (IB68)

Apolipoprotein E, also known as APOE, is a gene that suppresses the spread of melanoma and is involved in anti-tumor immune responses. 60% of the population has APOE in its most common form, the APOE3 allele, but the other 40% of the population has APOE2 or APOE4. Unlike APOE3, APOE2 and APOE4 negatively impact the immune response against melanoma, and individuals with APOE4 are at greater risk of developing atherosclerosis and Alzheimer’s. These alleles can create such different responses by coding for proteins that differ by just one or two amino acids, which as we learned in AP Biology, can make a big difference in how a protein is structured and functions.

After studying APOE’s impact on the immune response against melanoma, Sohail Tavazoie’s lab at The Rockefeller University grew curious to research if APOE variants impact COVID-19 outcomes. By testing on 300 mice with a mouse-adapted version of SARS-CoV-2, they found that mice with the APOE3 allele were more likely to survive than those with the APOE2 or APOE4 allele. Mice with APOE2 or APOE4 had a less effective immune response, causing more virus to replicate in their lungs, more inflammation, and more tissue damage. The researchers further demonstrated APOE’s impact by analyzing 13,000 patients in the UK Biobank and discovered that patients with two copies of APOE2 or APOE4 were more likely to have died of COVID-19 than those with two copies of APOE3.

With more studies done in the future, clinicians should prioritize that individuals with these alleles receive not only COVID-19 vaccinations and boosters, but also antiviral therapies if they get infected. If testing for which APOE allele you have sounds important to you, you can easily get genetic testing with a saliva sample or a blood test in a commercial lab.

Next Time You Think Losing An Hour Or Two Of Sleep Won’t Hurt… Think Again.

We’ve all been there. It’s a busy week, it’s getting late, and you’re tired, but you still have a lot to do for tomorrow.

A Cartoon Man Sleeping At Work

You convince yourself that if you sacrifice your sleep during the week and make it up on the weekend everything will be okay. Right? Well, unfortunately, according to the Mount Sinai School of Medicine, quite the opposite is true.

Research completed by Mount Sinai Hospital demonstrates that reducing the amount of sleep you get each night can lead to an increased risk of inflammatory disorders and heart disease. The researchers monitored 14 healthy adults that normally sleep 8 hours a night and had them sleep 6-7 hours for 6 weeks. They then drew and analyzed their blood, finding an increased number of immune cells, many of which did not function properly to protect against infections. An increased number of immune cells may seem beneficial, but in reality, if the number gets too high, immune cells can overreact and create inflammation. The DNA structure of the cells was also altered, which provides evidence for their decreased ability to defend against illnesses.

The researchers continued the study with testing on mice and found that even after having sleep recovery time, the mice still had changes in their immune system. The mice’s immune cells were rewired and reprogrammed to function under the stresses of having disrupted sleep, producing more white blood cells, which put the mice at a greater risk of having inflammation or a disease. These results serve as evidence to prove that sleep recovery cannot reverse the effects of lack of sleep.

Diagram of a white blood cell CRUK 028

The cells experience this change due to limited time to repair injured cells. As we sleep, our bodies turn their attention to our immune system, repair damaged cells, and release growth hormones. When we have disrupted or limited sleep, our bodies are not able to carry out these functions, causing greater susceptibility to health problems. It is important that our cells are able to complete their tasks, and it’s even more important that we can remove and replace cells that cannot. As we learned in AP Biology, the lysosome plays a major role in helping damaged cells perform apoptosis (programmed cell death). If our bodies are not given the time to carry out apoptosis and replace old damaged cells with new immune cells, our bodies are at greater risk for metabolic abnormalities and replication errors, connecting sleep deprivation to disease risk. So the next time you’re thinking of sacrificing sleep to do work, I hope you remember the health consequences and reconsider your decision 🙂

 

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