BioQuakes

AP Biology class blog for discussing current research in Biology

Author: samosome

CRISPR can help in the detection of Kidney Rejection sooner than you thought

 

 

Kidney Transplant

Diagram of a Transplanted Kidney

As of now, the only way to diagnose acute rejection is through a biopsy. This procedure can only detect problems when they are in a late stage. Doctors would be able to begin anti-rejection medication sooner if there was a way to non-invasively diagnose kidney rejection at an early stage. Well, there might be now….

 

Researchers have found an early warning sign of rejection in the urine of kidney transplant patients, a cytokine protein called CXCL9. Currently, the method used for measuring the protein (an enzyme-linked immunosorbent assay, or ELISA)  has been unsuccessful. However, Jonathan Dordick and colleagues have been working to develop a better technique. 

 

Kidney Transplant

How CRISPR works

They have based their new detection method on a gene-editing technology called  CRISPR/Cas12a. The CRISPR/Cas12a enzyme cuts a probe to produce a fluorescent signal when in the presence of the CXCL9 protein. Then by attaching a DNA barcode that aggregates a large number of CRISPR/Cas12a molecules, they were able to boost the fluorescent signal. This then led to an antibody that recognizes CXCL9. 

 

Another essential thing to note is that, unlike different CRISPR-based detection methods, the use of PCR amplification is not required. This makes it easier to modify to a device that could be used in more accessible ways, like in a doctor’s office or at home. When tested, the new system accurately measured CXCL9 levels for 11 kidney transplant patients. Since the immuno-CRISPR system is about 7 times more sensitive than an ELISA, kidney rejection can now be detected early. 

Stop Mice-ing Around Gene Editing in Mitochondria Is Now Possible

Mitochondria is often nicknamed the powerhouse of cells. It consists of a double membrane, DNA, ribosomes, inner membrane surface area fold called cristae, an inner fluid-filled space called the matrix. Mitochondria can self reproduce and can move around cells and change shape. It is also the site of cell respiration.  

Mitochondrion structure

Structure of Mitochondrion

Mitochondrial DNA makes up only 0.1% of the human genome and is passed down exclusively from mother to child. There are around 1,000 copies of mitochondrial DNA in each cell.  A cell is heteroplasmic if it contains a mixture of healthy and faulty mitochondrial DNA. If a cell has no healthy mitochondrial DNA, it is homoplasmic.

 

Mistakes in mitochondrial DNA affect how well the mitochondria work. Often more than 60% of the mitochondria in a cell will need to be damaged or mutated for mitochondrial diseases like mitochondrial diabetes to emerge. These diseases are often severe and, in some cases, fatal. They affect around every 1 in 5,000 people. These diseases are incurable and largely untreatable. Well until now….

 

The MRC Mitochondrial Biology Unit at the University of Cambridge found a possible answer in 2018. They used an experimental gene therapy treatment in mice. There they discovered that in heteroplasmic cells, they were successful in targeting and eliminating faulty mitochondrial DNA. Dr. Michal Minczuk shares that this new research does come with a catch, “It would only work in cells with enough healthy mitochondrial DNA to copy themselves and replace the faulty ones that had been removed. It would not work in cells whose entire mitochondria had faulty DNA.” 

 

Pedro Silva-Pinheiro tells us, “This is the first time that anyone has been able to change DNA base pairs in mitochondria in a live animal. It shows that, in principle, we can go in and correct spelling mistakes in defective mitochondrial DNA, producing healthy mitochondria that allow the cells to function properly.” He, along with Dr. Minczuk and their other colleagues, have also used a biological tool known as a mitochondrial base editor. They use this to edit the mitochondrial DNA of live mice. The treatment works by it being delivered into the mouse’s bloodstream using a modified virus. It is then taken in by its cells. The editor looks for unique combinations of the A, C, G, and T molecules that make up DNA.  Next changes the DNA base, changing a C to a T. Mitochondrial base editor can correct inevitable ‘spelling mistakes’ that cause the mitochondria to malfunction.

 

A recent example of how this research had been used is mitochondrial replacement therapy, or other known as three-person IVF. Mitochondrial replacement therapy replaces a mother’s defective mitochondria with a healthy donor’s. However, this process is extraordinarily complex and happens in fewer than one in three cycles in standard IVF.

 

The Key to SARS-CoV-2 Survival

Can your chance of surviving SARS-Cov-2 be predicted? It sure can be due to recently combined research efforts by ISB, Fred Hutchinson Cancer Research Center, Stanford University, Swedish Medical Center St. John’s Cancer Institute at Saint John’s Health Center, the University of Washington, the Howard Hughes Medical Institute. It comes from studying your immune system and a special part of your endocrine system, your metabolism

The researchers sampled the blood of nearly 200 COVID-19 patients. They took two draws per patient during the first week after being diagnosed with SARS-CoV-2 infection, totaling 374 blood samples. The researchers then analyzed their plasma and single immune cells. The analysis included 1,387 genes involved in metabolic pathways and 1,050 plasma metabolites. 

“We analyzed thousands of biological markers linked to metabolic pathways that underlie the immune system and found some clues as to what immune-metabolic changes may be pivotal in severe disease,” says researcher and graduate student from Fred Hutchinson Cancer Research Center, Jihoon Lee. Well, what were these clues? The clue is the link between how certain metabolic changes regulate how immune cells react when it comes to disease severity and predicting patient survival. Basically, increased COVID-19 severity leads to increased immune-related activity. 

Image drawn by author

With these new discoveries, researchers used single-cell sequencing to further investigate. They found that each major immune cell type has a distinct metabolic signature. “We have found metabolic reprogramming that is highly specific to individual immune cell classes (e.g. “killer” CD8+ T cells, “helper” CD4+ T cells, antibody-secreting B cells, etc.) and even cell subtypes, and the complex metabolic reprogramming of the immune system is associated with the plasma global metabolome and are predictive of disease severity and even patient death,”  says Dr. Yapeng Su, a research scientist at Institute for Systems Biology.

Despite the need for more advanced single-cell multi-omic analysis, this research has proven to be very successful. It provides significant insights for developing more effective treatments against COVID-19. What do you think about this research being used for predicting survivability for other diseases to come? 

Your Inner Chimpanzee

 

Chimpanzees

What is the closest living relative we have (evolutionary speaking)? That’s right, chimpanzees!! Our evolutionary paths separated us about five to six million years ago leading to the chimpanzee of today, and us humans of the 21st century, but we still have much in common. Like humans, Chimpanzees use body language to communicate. They often kiss, hug, pat each other on the back, hold hands and shake their fists. They even laugh when they get tickled. At the same time, a lot has also changed. Not only do we stand on two legs and are relatively hairless, but we also have brains that function differently. 

 

Recent research from Lund University has found the answer to what in our DNA makes our brains different. Created by Shinya Yamanaka, the study used a revolutionary stem cell technique. Yamanaka discovered that if reprogrammed specialized cells can be developed into all types of body tissue. It was even recognized by the 2012 Nobel Prize in Physiology or Medicine. 

 

The researchers used stem cells grown in a lab. Their partners in Germany, the US, and Japan reprogrammed the skin cells. Then Johan Jakobsson, professor of neuroscience at Lund University, and his partners examined the stem cells that they had developed into brain cells. Using the stem cells, the researchers specifically grew brain cells from humans and chimpanzees and compared the two cell types. The researchers then found that humans and chimpanzees use a part of their DNA in different ways. This appears to play a significant role in the development of our brains.

 

What the researchers learned was different in part of our DNA they and I found so unexpected. Unlike previous research in the part of the DNA where the protein-producing genes are — about roughly two percent of our entire DNA, the difference that was found indicated that the differences between chimpanzees and humans appear to lie outside the protein-coding genes. The research found that it is actually located a so-called structural variant of DNA in what has been labeled as “junk DNA,” a long repetitive DNA string that has long been deemed to have no function. This was thought to have no function. 

 

This data suggests that the basis for the human brain’s evolution is a lot more complex than previously throughout genetic mechanisms, as it was supposed that the answer was in that 2 percent of the genetic DNA. These results indicate that the overlooked 98 percent is what has been significant for the brain’s development is instead perhaps hidden in, which appears to be important. 

 

Researchers hope to answer that question one day. But there is a long way to go before they reach that point. The question that now remains is instead of carrying out further research on the two percent of coded DNA should they delve deeper into all 100 percent. Even though exploring the missed ninety-eight percent is a considerably more complicated task for research. 

 

One question that also definitely still remains is why did the researchers want to investigate the difference between humans and chimpanzees in the first place?  

 

Well, Johan Jakobsson believes that in the future the new findings will prove his belief that the brain is the key to understanding what it is that makes humans human. How did it come about that humans can use their brains in such a way that they can build societies, educate their children and develop advanced technology? It is fascinating!” (Lund University). He hopes that this research will contribute to answers about things like genetically-based questions about psychiatric disorders, such as schizophrenia. As for me, I wonder if this continued research will tell us anything about how Chimpanzees will evolve. 

 

 

Powered by WordPress & Theme by Anders Norén

Skip to toolbar