New method uses DNA barcodes for high throughput RNA and protein detection in deep tissue

    Recent developments in molecular biology have enabled unprecedented detail probing of tissues and cells, but examining deep tissue structures, particularly at the RNA and protein levels, remains a difficulty. Researchers have tried to develop techniques for identifying and measuring these biomolecules in dense, complicated tissue samples. However, a revolutionary new strategy has evolved, promising more efficient and precise detection: utilizing DNA barcodes for high-throughput RNA and protein identification in deep tissue.

    This new approach, which uses DNA barcodes to identify RNA and proteins, promises to transform how scientists examine deep tissues. With its high throughput, sensitivity, and capacity to maintain tissue architecture, it offers up new avenues for studying complex biological systems. This discovery, whether for academic research or clinical applications, represents a tremendous step forward in molecular biology, bringing us closer to solving the mysteries of deep tissue biology and improving human health outcomes.

Shedding Light on Cancer Treatment

 Lightspeed to a Cancer-Free Era

Cancer treatments have been improving year after year leaps and bounds for the last few decades, and another milestone was hit today. A lab in Ohio State found a way to break up the structures of mitochondria by inducing light-activated electrical currents inside the cell. They dubbed the technique mLumiOpto. According to the results of the research this causes "programmed cell death followed by DNA damage." To do this they implant the genetic information of a light-sensitive protein known as CoChR, which carries a positive charge, and a bioluminescent enzyme. They follow that injection with the injection of an unnamed chemical that induces the bioluminescence, and thus activates CoChR, inducing mitochondrial collapse. To ensure that the virus doesn't target host cells, they use "well-characterized adeno-associated virus (AAV)" which has a low infectious characteristic. As the team is well versed in dealing with cancer cells, they decided to refine the process and add a promoter protein to increase the growth of CoChR in the cells. They innovatively use a monoclonal antibody that is geared to detect the specific receptors found in cancer cells. 

This research is phenomenal. I can't wait to see what cancers they are capable of treating in the future, it is unfortunate they patented the technology, and I can only hope that they are doing that so nobody else can price gouge it and that they will release the procedure for a low cost to help save lives. Building off of this could be used for non cancerous tumors possibly, depending on the cell surface receptors found in those cells, leading to a revolution in our cell-specific targeting for diseases and other maladies. Big congratulations to Ohio State for this one, as well as the researchers involved in the project: Lufang Zhou, Margaret Liu, Kai Chen of Liu's lab and Patrick Ernst of Zhou's lab, Anusua Sarkar, Seulhee Kim, Yingnan Si, Tanvi Varadkar and Matthew Ringel. All involved were from Ohio State.

Links

https://www.sciencedaily.com/releases/2024/12/241213125202.htm

https://www.biotechniques.com/cancer-research/let-there-be-light-gene-therapy-targets-cancer-cells-mitochondria/

tRNA as a function of energy production

 

A mitochondrial study unveiled new insights in how our cells use tRNA for the process of energy production. Researchers from the Karolinska Institutet, with the help of cryo-electron microscopy, have been able to identify the mechanism of mitochondrial tRNA 3’ processing by the enzyme RNase Z. The exact process of tRNA in mitochondria was not fully well understood, but with this study how the RNase Z complex recognizes and process tRNA molecules. It was discovered that there is a 5’ to 3’ processing order of the tRNAs, which makes sure that they are correctly prepared for protein synthesis. The researchers declared the directionality of tRNA as a crucial part of the process.

When thinking of tRNA, whether in mitochondrial processes or not, we understand its importance in the function of cells and organisms. Problems in the processing of these transport sequences can lead to serious mitochondrial diseases. Another study done by researchers from Kumamoto University revealed the critical role that tRNA has in modifying enzymes in the brain. By creating the absence of the TRMT10A gene in different mice subjects, the researchers encountered a decreased level of measured tRNA levels in the brain. Most specifically, in the initiator methionine tRNA, and glutamine. This process diminished protein synthesis and compromised the structural integrity of the synapses, leading to impaired cognitive abilities.

In my opinion, both studies show the importance of tRNA as part of the cellular process and its importance in the structural integrity of our making as organisms that can think and express ourselves. Furthering our understanding of the mechanisms behind tRNA in mitochondrial processes and energy production can lead us into having solutions for different genetical processes. We understand that failures in the tRNA messaging can lead to disease and cognitive disorders, and we also recognize now that without specific genes and enzymes that support our brain function, our tRNA can be compromised and so can our health. Understanding the mechanisms and consequences of tRNA and its implications in the human body is of crucial importance to me and it should be to everyone.

Sources:

https://medicalxpress.com/news/2024-09-reveals-critical-role-trna-enzyme.html

https://phys.org/news/2024-11-mitochondrial-insights-cells-rna-energy.html#google_vignette

A protein found in human sweat may protect against Lyme disease

In this article written by Anne Trafton, the author discusses how researchers have discovered a protein in human sweat that can protect against Lyme disease. They hope to use this discovery to develop skin creams to prevent the disease or treat infections that don't respond to antibiotics.

The researchers ran a genome-wide association study to find genetic markers of disease susceptibility. They discovered SCGB1D2, a secretoglobin primarily produced by sweat glands. They exposed SCGB1D2 and a mutated version of the protein to the bacteria that causes Lyme disease and discovered the unmutated version significantly inhibited its growth. They then injected mice with the bacteria, along with the mutated and unmutated protein. The mice with the unmutated protein did not become infected, while the ones with the mutated proteins did.

I found this article to be quite interesting. I was exposed to Lyme disease as a kid, so seeing new research about it is intriguing. I do think the notion of a preventative cream, though interesting, is unrealistic. I'm unsure how many people would routinely use a cream whose sole purpose is to help prevent against Lyme disease. I think a better course of action would be to add it to insect repellants. I do however hope the cream will be able to help people with antibiotic-resistant bacteria. Living with Lyme disease is incredibly difficult. 

Article: A protein found in human sweat may protect against Lyme disease

Additional Link: A protein found in sweat may protect people from Lyme disease

Secretoglobin SCGB1D2 found in human sweat may protect against those affected by Lyme's Disease

     Lyme's disease affects more than 500,000 people a year, the disease is carried by mice, deer, and other animals and is transmitted by ticks. The disease is caused by the bacterium Borrelia Burgdorferi, which can cause symptoms like fatigue, body aches, fever, and other symptoms that can usually be cleared up but, for others, these symptoms may linger for years. Michal Caspi Tal and Hanna Ollila, researchers at MIT, ran a genome-wide association study (GWAS) with included genome sequences for 410,000 people, 7,000 of them having Lyme's disease. The article described how the GWAS revealed how the secretoglobin, a family of proteins that play a role in immune responses to infection, SCGB1D2 (mainly produced by sweat glands) may be linked to the disease. Mice injected with borrelia burgdorferi exposed to a mutant version of the protein fell victim to the disease however, mice injected with borrelia burgdorferi exposed to the normal version of the protein showed no signs or symptoms of the disease. Though researchers are not sure how the protein inhibits bacterial growth, they found that the mutated version causes a shift from the amino acid proline to leucine. 

    I found the research that was done to be potentially life changing for many people. So many people suffer from Lyme's disease and is very common around woody areas, like the pinelands. The potential that has risen from these findings, as talked about in the article, could eventually be used to make protective creams, or new medicines for people whose symptoms are still around, even after antibiotics. The new information could also potentially be applied to dogs, another species commonly affected by the bacterium. I think it's amazing what could be found using huge genome databases. 

Article: A Protein found in human sweat may protect against Lyme disease

Reference: SCGB1D2 inhibits growth of Borrelia burgdorferi and affect susceptibility to Lyme disease

Gene Mutation Linked to Esophageal Cancer

 Esophageal Cancer affects the throat and typically begins in the cells lining the esophagus. It is more common in men than in women. Symptoms include difficulty swallowing, weight loss, chest pain, indigestion, and coughing. Smoking tobacco and alcohol use can be risk factors for developing it. The exact cause of esophageal cancer is unknown but mutations in the cell's DNA cause the cells to grow and divide rapidly, resulting in cancerous cells. There are 2 main types of esophageal cancer, adenocarcinoma being the most common. Esophageal cancer is the sixth most common cause of cancer deaths. Recently, researchers have found a gene mutation linked to esophageal cancer, specifically esophageal adenocarcinoma. Being able to identify the gene mutation allows those with a high risk of developing the cancer to find treatment strategies before it is too late. Researchers studied patients with the disease and found that the gene Caveolin-3 (CAV3), is related to the cause of the gene mutations in the cell. Cavoleins are components of a cell that deal with the regulation of the proteins involved in the cell's proper function. Specifically, CAV3 cells are found in mucosal glands. When esophageal cells are injured, such as from smoking or acid reflux, these cells come to the surface to repair the damaged proteins. With an inherited CAV3 mutation, the cells are not able to heal properly and can cause adenocarcinoma. I found this article to be extremely interesting. A small mutation in a specific part of the cell can cause drastic damage to the body. More research needs to be done to identify other possible causes of different types of esophageal cancer.

Mouse Bites Are Potentially Venomous Like Snakes

 

In this article, the OKINAWA INSTITUTE OF SCIENCE AND TECHNOLOGY (OIST) GRADUATE UNIVERSITY, discusses the origins and molecular make up of venom, and how evidence shows mammal salivary glands and snake venom glands share a common genetic foundation.the team searched for genes that work alongside and interact strongly with the venom genes. The scientists used venom glands collected from the Taiwan habu snake from Asia. Agneesh Barua said, "The role of these genes in the unfolded protein response pathway makes a lot of sense as venoms are complex mixtures of proteins. So to ensure you can manufacture all these proteins, you need a robust system in place to make sure the proteins are folded correctly so they can function effectively.". 

It seemed that other mammals like humans, dogs, and rodents also have their own version of these genes in the same pattern. Due to this, scientists believe this supports the theory that that venom glands evolved from early salivary glands. In a few thousand years we might encounter an evolutionary event where mice and even humans are venomous and this is definitely something worth studying further for the future of our ecosystem and understanding the evolutionary effects in genetics.

Links:

https://scitechdaily.com/startling-new-evidence-shows-a-mouses-bite-holds-venomous-potential/

https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/snake-venom#:~:text=Abstract,venom%20secreted%20by%20oral%20glands. 

APOE gene and Susceptibility to COVID-19

 Subject: APOE gene, Alzheimers and COVID-19

Article: Genetics risk factors for Alzheimers also raise the risk of getting COVID-19 

When it comes to the susceptibility of contracting COVID-19, recent tests during the pandemic have stated that two versions of the APOE gene had been the cause. The general function of the APOE gene is to provide the instructions to make lipoproteins which are responsible for there being a healthy level of cholesterol in the body to prevent a clotting, a heart attack, or strokes. It is most common for people to have the APOE3 gene then the APOE4 gene.  People with the APOE4 gene are more likely to develop early onset Alzheimers if both copies of the gene are present and therefore they are more likely to contract the corona virus than those with APOE3 gene. The studies showed that people with dementia and carried the APOE4 allele were also more susceptible to serious symptoms of the virus compared to those with APOE3 and those with a copy of each gene are less likely to contract the virus compared to those who have both APOE3. So far it is not known why it's the case. But because the APOE gene provides instructions to make proteins it should be further looked into if their proteins have nothing to do with antibodies since they are carried in the blood and are able to recognize pathogens. Further studies could lead to what other susceptible diseases are as a result of having either versions of this gene. 

 Article link: https://www.sciencenews.org/article/coronavirus-covid-19-genetic-risk-factors-alzheimers-diseas

Supporting link(s): https://medlineplus.gov/genetics/gene/apoe/#:~:text=The%20APOE%20gene%20provides%20instructions,carrying%20them%20through%20the%20bloodstream. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3384159/#:~:text=ApoE4%20contains%20an%20arginine%20residue,with%20respect%20to%20this%20disease. 

Main Source: https://www.sciencenews.org/topic/genetics

Got To Go? Scientists Uncover A Gene That Helps Sense A Full Bladder

 

Research scientists at The Scripps Institute in La Jolla, CA, discovered the gene responsible for making us urinate! Sounds really gross, but have you ever wondered why you always have a powerful urge to urinate. The gene that is responsible is the PIEZO2, which is kind of funny because it has "pee" in it. This gene is located in sensory neurons as well as the urothelial cells that help coordinate urination (Nature). These two cell types all the brain to know when we need to pee. It makes sense why the urge is so powerful because urinating is essential to our health. We need to get rid of the waste in our body and holing it in can cause damage to our health. This gene allows us to stay healthy, by letting us know, kind of like an alarm clock, when we need to release our waste. The neurons and cells work together to form the urge. When we have to pee, our bladder expands and this is hen the PIEZO2 genes that encode the proteins that are activated. An experiment with mice showed that removing the gene cause the mice to have trouble urinating, in which they urinated at randoms times not in a controlled way. Without this gene, we might be peeing randomly which is not something you would ant to see in public. They are conducting more research for the future to gain a better understanding.

https://www.genengnews.com/news/got-to-go-scientists-uncover-a-gene-that-helps-sense-a-full-bladder/

https://neurosciencenews.com/urination-genetics-17187/

6,000 Antibiotic Resistant Genes Found in Human Gut Bacteria

The human gut inhabits more than a trillion microorganisms, with most of the residents being bacteria. Although most bacteria in our gut are beneficial to us, a recent study has identified more than 6,000 antibiotic resistant genes in the bacteria living within our gut. The study, conducted by the Institut National de la Recherche Agronomique (INRA) in collaboration with Willem van Schaik of the University Birmingham, developed a new method to identify resistant genes in the human gut. The researchers compared 3-D structures of known antibiotic resistant enzymes to proteins produced by gut bacteria. The same method was then applied to a catalogue of several million genes in the human gut and the genes were compared. Comparisons have shown that the antibiotic resistant genes in gut bacteria are extremely different compared to previously identified resistant genes in pathogenic bacteria.

The study highlights that there is an immense diversity in antibiotic resistant genes in the human gut environment. Although these genes have a harmless relationship with the human host (for now), the bacteria can pose a threat for those who are hospitalized or immunocompromised as they do not have the immune strength to combat bacteria resistant to antibiotics. Continuing use of antibiotics may also lead to resistant genes in gut bacteria being transferred to pathogenic bacteria, rendering the effectiveness of antibiotics dramatically. Although the transfer of resistant genes to pathogenic bacteria is rare, it is not impossible and continued overuse can potentially raise the chances of these pathogenic bacteria receiving the genes.

I believe this study is very interesting, especially since I am passionate about antibacterial and antibiotic resistance. The study has stated that the mechanisms of how gut bacteria receive antibiotic resistant genes are still unknown, but results give some insight on how genetics between resistant genes differ from gut bacteria to pathogenic ones. I hope in the future we can find a way to tackle antibiotic resistance, especially through thorough understanding of the genetics and evolutionary biology of bacterial specimens (both good and bad). 

Links:
https://www.birmingham.ac.uk/news/latest/2018/11/antibiotic-resistance-drugs-gut-bacteria.aspx
https://www.genengnews.com/news/the-human-gut-resistome-contains-over-6000-genes/
https://www.researchgate.net/publication/329192381_Prediction_of_the_intestinal_resistome_by_a_three-dimensional_structure-based_method

Using E.Coli to find cancer promoting proteins in humans

           Cancer results from the overproduction of mutations in the cell, which proceeds in the damage of the DNA. There are external events such as smoking and sunlight that damages DNA, but it is mostly an internal occurrence. A study conducted in BaylorCollege of Medicine and the University of Texas of Austin was proceeded to determine proteins that are cancer-promoting by using the bacteria E.coli as a model. Due to the bacterium E.coli having similar biological process with humans, Rosenberg—the leader of Cancer Evolvability Program—set out to uncover proteins that cause damage in the DNA in ways that can eventually lead to cancer.

            The team genetically modified E.coli to over express 4,000 bacterial genes. When the protein overproduction then turned fluorescent red this showed how it was associated to DNA damage. It was founded that the DNA that was damaged were not directly related to the DNA, but instead the transport of molecules across the cell membrane. It showed that the overproduction of E.coli proteins not only caused damage to the DNA but increase of mutations.

            This research can tell be used to further broaden our information in how there is many different ways that DNA can be damaged. By researching more in this topic we can then find ways to prevent or slow down ways of those that causes cancer. There could also be ways to protect our genomes from being harmed.

Cell biology of microtubules

Microtubules are also known as filamentous polymers. Microtubules play a role in the segregation of chromosomes and molecular transport. Research has been done to examine various lengths of microtubules in response to the changes of their proteins. Microtubules are outer cylinders that secure protofilaments consisting of tubulin proteins and serve as an intercellular transport network by providing mechanical stability.

Scientist, Erwin Frey, stated that as microtubules elongate, the greater the number of motor proteins will accommodate. These motor molecules are called kinesins, which proceed along the protofilament. Kinesin proteins move toward the positive end of the microtubule, while the motor protein moves toward the negative end. When the kinesin protein reaches the end, it detaches from the filament and takes the tubulin, thus allowing another tubulin to bind to the end. In certain ranges, the growth and shrinkage of the microtubules operates as it would if resources were not limiting. However, components and resources within a cell are unlikely to be available in unlimited amounts. Therefore, there is a certain length at which the rates of growth and shrinkage balance out.

Microtubules play an essential role in the cell, for they allow for the segregation of chromosomes. Having kinesin proteins allow for the microtubule to elongate and perform its function to the cell.

For additional information, refer to the original article.

For information on microtubules and protein functions, refer to link1 and article1.

The Doorbell to the cell (GPCRs)

G-protein-coupled receptors (GPCRs), in humans we have over 8000 of them. Located on the membrane in eukaryotes, these receptors are like a mailbox for different inputs of proteins, sugars, fats (lipids), and light energy. (2) They take in information from either other cells and convey them or information of nutrients. (1) This is a very simplified explanation of that they are and what they do (watered down). These receptors are becoming more important to medicine and pharmaceuticals with being able to understand their function and "how some researchers believe that 1/3 to 1/2 of drugs bind to GPCRs. " (1)

         "It's a huge field of active research in academia and industry because if we can figure out precisely        how GPCRs work, then we can more easily design drugs to change their behavior and thereby                  control pain, hunger, and more," said coauthor Christopher Neale, a researcher with the Center for            Nonlinear Studies at Los Alamos National Laboratory. (2)

The Researchers have found that their is a doorbell structure that communicates to the cell of important nearby molecules. They believe that understanding this structure and the function of it will inevitably help in producing better medication. (1),(2),(3)

REFERENCES
(1) https://www.nature.com/scitable/topicpage/gpcr-14047471
(2) https://www.sciencedaily.com/releases/2018/04/180412102922.htm
(3) https://www.nature.com/articles/s41467-018-03314-9

Improvements made in DNA transfer in gene therapy

With research and development of genetically modified viruses, DNA has found a way to repair and replace defective genes in cells. Hereditary human diseases, such as Parkinson’s disease, Huntington’s disease, cystic fibrosis, are caused by genetic defects. One way to eradicate these traits is through gene therapy. Using gene therapy and the development of genetically modified viruses, DNA is introduced into cells to repair and replace defective genes. Scientist Jens Gruber hypothesizes that the production of viruses can efficiently boost exosome production in cells.

Scientist of the German Primate Center discover an efficient treatment for the cells. The cell like HEK293 is used for the production of therapeutic viruses. The protein, CD9, is produced in large quantities. This protein helps for cell movement, cell to cell contact, and membrane fusion. The modifications were made on the viruses used for gene transfer, for CD9 integrates into the envelope membrane of the cell. Such process produces faster and prevent further infection to the target cells. During gene therapy, defective genes are replaced with functional genes, which help prevent infection of the cell. Having the HEK293-CD9 cells allows for the exome production of CD9 proteins in the membrane, thus allowing for the improvement for DNA transfer. During the process, genes will be repaired and replaced using the proteins.

The results of the study show that the increased amount of CD9 protein resulted in higher infection. As researchers further investigate, their future findings may be a solution to prevent infection to the cells. Although small problems arise during the study, researchers continue to find a way to enhance and make this improvement effective.

For further information, refer to the original article.

For additional information on genes and gene therapy, click on the following link1 link2.

Virus found to adapt through newly discovered path of evolution

Colleagues of the University of California San Diego has discovered a new path of evolution. They found a process that is previsously unseen in evolution. With these new finding they were doing research on how mutations arise to make transmission easy from one host to another and how genes acquire new functions. This could be applied to investagate virual diseases such as bird flu and Ebola. This was a step in the right direction for these researchers, they realized by learning how virsues achieve evolutionary flexibility they can have a new way of how to step up “road blocks” to stop new diseases from emerging.

Katherine Petrie led this project, the researchers used lamba, which is a virus that infect bacteria but not humans; this allows flexibility in lab testing. In the lab they were able to capture the evolutionary process in action. They found that the proteins mistakes allowed the virus to infect the normal host. Now the researchers are looking for eamples of their new discovered evolutionary epsidoe and to see how common this is.  

https://www.sciencedaily.com/releases/2018/03/180329141037.htm

http://ucsdnews.ucsd.edu/pressrelease/virus_found_to_adapt_through_newly_discovered_path_of_evolution