The molecular mechanisms of sleep

     Sleep, the one thing we all need and want but the bed is only comfortable during the middle of the day. However, while we know sleep is important for the human body, the scientific reason for this is still a mystery but a research group in Tokyo might have brought us a bit closer to the truth.

    Professor Hiroki Ueda at the Graduate School of Medicine of the University of Tokyo led a team to figure out what exactly causes mammals to sleep and wake up. In there research, they found three enzyme groups that held the answers they were looking for. The first was protein kinase A, PKA, that was observed to be responsible for wakefulness. PKA is activated by a cyclic AMP and when activated promotes kinase activity while inhibiting enzyme activity. This inhibited enzyme activity belongs to the next two enzymes, protein phosphatase 1, PP1, and calcineurin, both responsible for sleep. Both of these enzymes work with dephosphorylation and deactivate certain functions that result in sleepiness. These three enzymes were also observed to be competitive which explains why we eventually go to sleep.

    This is only a part of a greater puzzle since we still don't know how PP1 and calcineurin start dephosphorylation and how competitive these two are with PKA and I am kind of glad that it is. The more I learn about the human body and all of its ins and outs, the line between human and computer begins to thin. However, the thing that has always kept that line there was always the brain, or mind, and how it is unpredictable. While it would be interesting to know how sleep works and its reason for our bodies, I think I can sleep happy without that knowledge, provided its the middle of the day. That's a question we should answer, why does a nap feel so much better than an actual night sleep.

Creating Synthetic Enzymes: Engineering Disease Treating Mechanisms

 A bioengineer at the University of Texas at Dallas has successfully developed synthetic enzymes that can control the behavior of Vg1, a vital signaling molecule in the embryonic development of muscle, bone, and blood in vertebrates.

In general, learning about the molecular rules governing signal formation provides better insight into how disease-treating and disease-curing mechanisms can be developed. In this case, researchers studied the formation of Vg1 in zebrafish embryos. Researchers were interested in learning about how synthetic enzymes could control natural proteins, hoping to build biological circuits that could imbue introduced cells with new functions like cancer detection or disease resolution at the molecular level. Zebrafish were found to be an ideal model organism since they have 70% similarity to the human genome and were small enough to grow and observe under a microscope. Additionally, researchers studied the molecular interactions between Vg1 and protein Nodal, finding that they could not interact with one another due to certain chaperone-like proteins that bind to and inactivate Vg1.  Developing synthetic cleaving enzymes from a family of viruses, researchers used these to cut specific Vg1 amino acids that would activate signaling on target cells.

It was rather interesting to learn about how synthetic proteins (or enzymes rather) can have an influence on and control certain signaling proteins to direct a mechanism involving disease identification and treatment. Through this insightful research, it may be possible to integrate various functions related to those two concepts and make treatments much more efficient.

For more information regarding the information gathered, the article has been linked here and the published research study has been linked here.

Thousands of DNA- Cutting Enzymes Found in Eukaryotes

 

Many eukaryotic organisms contain DNA cutting enzymes called Fanzors and scientists at MIT’s McGovern Institute for Brain Research have identified that there are thousands of them.  Fanzors are RNA- guided enzymes that can be programmed to cut DNA at specific sites and its diversity gives scientists a large set of programmable enzymes that could be adapted into new tools for research or medicine. These enzymes are much like bacterial enzymes known as CRISPR, bacterial enzymes that power the widely used gene editing system. CRISPRS have made clear how useful RNA guided enzymes can be when used in the lab. The CRISPR-based genome editing tools were developed by MIT professors and McGovern investigators. These editing tools have changed the way scientists modify DNA, accelerating research and enabling the development of a lot of different types of gene therapies. Fanzor enzymes can be programmed to cut specific DNA sequences and it has been discovered that Fanzors can target DNA sequences in humans without optimization. Fanzors likely evolved from the RNA-guided DNA-cutting bacterial enzymes called TnpBs. The traced evolutionary connections suggest that the TnpBs probably entered the eukaryotic cells, some had likely been transmitted by viruses and some were likely introduced by symbiotic bacteria. A feature that they had developed through evolution was having a signal that allows them to enter a nucleus of a cell, where they would have access to DNA. The research team determined that Fanzors evolved a DNA-cutting active site that is distinct from their predecessors. The active site seems to allow the enzyme to cut its target sequence more precisely than the ancestors of TnpB. When the other enzymes are targeted to a DNA sequence in a test tube, they become activated and cut other sequences in the tube, which is something that the Fanzors do not do. When the researchers used an RNA guide to direct the enzymes to cut specific sites in the DNA of human cells, it was found that certain Fanzors were able to cut the target sequences with about 10% to 20% efficiency. 

These new findings are very important as they could help with discovering different, sophisticated genome editing techniques. Hopefully, with the discovery of the diversity of Fanzors, enzymes naturally evolved in eukaryotes could be better suited to function safely and efficiently in other eukaryotes, including humans. This article was exciting to read because it indicates the promises of further discoveries of different editing techniques for DNA.

Sources:

https://news.mit.edu/2023/thousands-programmable-dna-cutters-found-algae-snails-other-organisms-1013 

https://news.mit.edu/2023/fanzor-system-in-animals-can-edit-human-genome-0628 

The Cause of Chewy Chicken Meat!

The Cause of Chewy Chicken Meat!

Almost everyone eats chickens, and ever wonder why some chicken meat is soft and some hard and chewy? Recently published, the University of Delaware researchers have discovered that lipoprotein lipase in chicken may contribute to wooden breast syndrome. Lipoprotein lipase is an enzyme that is important for fat metabolism. For decades, researchers have been studying wooden breast syndrome in broiler chickens that involved with analyzed genes in the disease and the identified biomarker for the disorder. The researchers also explain the hardened breast tissue from these chickens.

How did these researchers find that lipoprotein lipase is the answer? The researchers know that breast muscle fibers in chicken reply on sugar, which is a glucose molecule for fuel and not fat molecules in this case. They use RNA sequencing to determine which genes expressed, and finally, they found evidence of lipoprotein lipase expressed in endothelial cells. Since fat oxidized for energy in the breast, it causes another excess release of the free radical molecule that modifies the terrible fats and protein, which then causes a problem for the chicken’s immune system. This eventually leads to hard and chewy chickens.


This is a useful finding that researchers were able to discover. This would help growers manage to be more cautious about what they feed or look over how the conditions of the chicken are before actually going into the market, processed for meat, or breeds that may result in economic losses or disease spreading.


https://www.sciencedaily.com/releases/2019/11/191120175613.htm
https://eurekalert.org/pub_releases/2019-11/uod-tco112019.php

Teaching life a new trick: Bacteria make boron-carbon bonds

In article on Science Daily, researchers have developed a way to genetically engineer a enzyme in a bacteria that would create chemical compounds containing bonds between boron and carbon. This is essential because there has been no known life form that can produce the boron-carbon bonds because the bonds would be usually created by chemists in laboratories. The findings is part of a new wave of synthetic biology, which living organisms are taught to make "greener"chemical compounds needed for pharmaceuticals, agricultural chemicals and industrial products. Creating greener alternatives can be beneficial because they are more economical and would supposedly produce less toxic waste.

It is interesting how researchers are capable on creating more efficient and safer ways of producing chemicals from living organisms. This could be a new opening to more experiments like this, leading to synthetic made chemicals just from living organisms. With this, it could be possible that laboratory made chemicals could be abandoned or less depended on because of the toxins that are produced and for how much it costs to produce the chemicals. This could benefit many in pharmaceuticals and business.


https://www.sciencedaily.com/releases/2017/11/171129131417.htm

http://www.sciencenewsline.com/news/2017112921320019.html

Scientists discover enzyme that supports brain tumor growth

        A group of researchers from the University of Texas MD Anderson Center in Houston has discovered an enzyme that is found to assist in the growth of brain tumors. This finding can possibly be a big help to scientists trying to come up with new potential tumor treatment approaches. The observation here was that a specific enzyme - acetyl CoA synthetase 2 (ACSS2) is responsible for providing tumors with a route to survive. The ACSS2 allows production of cellular structures which aid tumor development.

        The head researcher, Zhimin Lu, Ph.D., (professor of neuro-oncology) and his colleagues used a gene editing tool called CRISPR to see what ACSS2 does in histone acetylation by generating acetyl CoA from acetate inside the nucleus of the cell. Just to clarify, "histones," are proteins that act as "spools" for DNA to wind around and are vital for gene regulation. Histone modification using a metabolic enzyme was found to be significant for cells to remain stable and for the development of tumors. 

    In the words of Dr. Lu, "These findings elucidate an instrumental interplay between reprogramming of metabolism and gene expression in cancer cells. Inhibition of both ACSS2's nuclear function and the metabolic pathway, known as glycolysis, which converts glucose to tumor-feeding energy, appears to be an efficient approach for cancer treatment." 

        This research and the enzyme discovery provides new information regarding nuclear translocation. It is very important and an exciting finding because it shows how ACSS2 can potentially be a player in new therapeutic approaches for treating cancer. With each new discovery, we are getting closer to finding the cure for cancer, making every single finding another step in the right direction! 

https://www.medicalnewstoday.com/articles/317654.php?sr

http://neurosciencenews.com/acss2-enzyme-brain-cancer-6775/