So I mentioned earlier this month that one of the ideas that had been floating around in my head last year was doing a weekly post summarizing all the science news I had read that week (and probably shared via Twitter or LinkedIn).
This will be the first in hopefully weekly (or possibly bi-weekly) installments of my Science News Round-Up. The topics are going to be bouncing around from cancer treatments to neurological disorder treatments, to DNA, RNA, protein, and probably everything in between.
As mentioned before–my top strength is learner, which means I love reading on different topics (and within science I hop between just about everything). Also these posts may lead to other spin-off posts as I will possibly be looking into various topics more deeply.
Also if I am able to download the paper that is mentioned in the article–they will automatically become a separate post and will show up at a later date (after I have time to read the paper and take notes). So, with that said basically all of the news round-ups will be over the news brief, background, but not the actual article.
Also–FYI this first one, is going to be a very long post (possibly a fifteen to twenty minute read).
The articles this week are all showcased on Genetic Engineering & Biotechnology News website. Their site is usually updated Monday thru Friday with new stories, and you can also subscribe to their newsletter and get their daily briefings.
One article this week was entitled “Strategy to boost CAR-T cell efficacy against solid tumors demonstrated in mice”.
A little background is probably needed:
CAR-T cells are white blood cells that have been genetically engineered to recognize and attack cancer cells that are expressing certain proteins on their surface.
The proteins on the surface of the cancer cells are the ‘antigens’ that the CAR-T cells recognize. This allows for the CAR-T cells to be ‘customized’ for different cancer types, and can be considered almost a ‘personalized’ treatment plan for cancer patients.
This treatment method has been successful for B-cell lymphoma and is in clinical trials for other blood cancers.
There are two problems with using this treatment for other types of cancers (outside of lymphomas) are 1) CAR-T cells have to get to the tumor site, and then 2) enter the tumor and be able to survive and replicate to kill off the cancer cells.
A group of scientists at the University of North Carolina may have found a way to increase the success rate of CAR-T cells when combined with other immuno-therapies.
They published their work “STING agonist promotes CAR-T cell trafficking and persistence in breast cancer” in the journal of Experimental Medicine. Again disclosure–I haven’t read the article, because it is behind a pay wall (where you have to pay to have access to the article). I’m hoping it will become freely accessible within the next six to eight months.
The key take away points from the news article were that by activating the STING pathway (which is an pathway that induces inflammation in response to a viral or bacterial infection), the CAR-T cells ability to destroy cancer cells in mice increased. In addition if the ‘checkpoint’ of turning off the CAR-T cells was inhibited, their ability to ‘stay on’ increased as well.
They then came up with a triple combination: CAR-T cells derived from either Th17 or Tc17 cells (T-cells that had longer persistence in the tumor micro-environment), use of therapeutic antibodies to deplete various immuno-suppressive cells from the micro-environment, and turning off the CAR-T ‘check-point’ allowed for these CAR-T cells to destroy breast cancer cells in mice.
To be able to translate these results to human trials, a different agonist for the STING pathway would be needed (as the one used in mice doesn’t activate the pathway in humans). Plus, one would need to see which cancer could be treated with activating the STING pathway. The group stated that they would initially focus on improving treatments for head and neck cancers first, and if the combination is beneficial, move on to other cancers.
CAR-T image came from: https://blog.dana-farber.org/insight/2018/20/recurrence-remission-lymphoma-patient-cancer-free-car-t-cell-therapy/
The second article I read was titled “RNA-DNA World Circumvents RNA World Sticking Point”.
This article covered the sticky question–which was first DNA or RNA?
Scientists at the Scripps Research Institute published their paper “Prebiotic Phosphorylation and Concomitant Oligomerization of Deoxynucleosides to form DNA” in the journal Angewandte Chemie. Again–I haven’t read the paper, because it is behind a pay wall.
What the group found though is that through the combination of two chemicals (diamidophosphate and 2-aminoimidazole) that were probably also present in the ozone of Earth’s early atmosphere, along with various nucleotides, you can end up with a RNA-DNA chimera.
This chimera then allowed each ‘strand’ to somewhat easily disassociate from the other to replicate, but at the same time forming a chimera from time to time for stability.
The RNA-world hypothesis is based on the idea that RNA was the original self-replicating molecule. The only ‘sticky’ problem with this hypothesis is that when RNA binds to itself (forming a double-stranded molecule), it is very difficult to pull them apart without the help of enzymes (which wouldn’t have been present at early in Earth’s formation).
The chimera RNA-DNA gives support to the hypothesis that maybe DNA and RNA co-emerged at roughly the same time.
This discovery (that the interaction of these two chemicals and various nucleotides can lead to synthesis of DNA) leads to another question–could there now be a broader impact on science? Could the use of these two chemicals possibly make various things easier and cheaper? Such as developing an enzyme-free method of making DNA & RNA, which could then lead to revamping how we do PCR reactions or even synthesize various oligo nucleotides for research.
Image of the RNA-DNA world hypothesis from: https://phys.org/news/2019-09-rna-dna-rna-dna-chimeras
The third article that I read this past week was “Single-cell transcriptome profiling of gastric tumors reveals prognostic gene signatures”.
One major problem with all forms of cancers is the heterogeneity of the tumors. While people can have the ‘same type’ of cancer–for example, breast cancer–each cancer is actually slightly different due to the individual mutations of each patient.
This is why developing cancer treatments are so difficult–they may not (and often do not) work for every patient with that particular cancer. This is one reason why there has been such a push for individualized cancer treatment plans.
So a group of scientists at the University of Texas MD Anderson Cancer Center, were able to use single-cell sequencing to look at the individual transcriptome of cancer cells from 20 patients who had/have advanced gastric cancer.
Their article “Single-cell dissection of intratumoral heterogeneity and lineage diversity in metastatic gastric adenocarcinoma” was published recently in Nature Medicine. Again, I have not read the article because it is behind a pay wall (hopefully will be available freely in about six to twelve months).
They collected ascites fluid (which is the fluid that accumulates in the abdominal cavity due to liver disease, cancer, and/or heart failure), from these patients and then isolated a specific cancer cell: peritoneal carcinomatosis cells. These are a specific cancer cell that invades the abdominal cavity, adhering to the stomach and other organs.
They isolated, profiled, and sequenced 45,048 peritoneal carcinomatosis (PC) cells. They learned that the cells seemed to have one of two lineage origins: gastric (stomach) and were considered the most aggressive PC cells resulting in a shorter survival prognosis, or intestinal-like, which were less aggressive, allowing patients to have a longer survival rate.
Through the profiling of the 45,048 cells, they were able to isolate a signature pattern of 12 genes that could be correlated to patient survival, which they tested against even more data from more patients who have PC.
They are hoping that the profiles of the PC cells may also give rise to potential targets for treatment, as there is currently no effective treatment for patients who have peritoneal carcinomatosis.
Cartoon on single-cell sequence came from: https://en.wikipedia.org/wiki/Single_cell_sequencing
The next article was one I found really interesting: “MicroRNAs modulating diurnal rhythms in cells identified in genome-wide study”.
I found this article fascinating in part to the fact that microRNAs were the topic of my dissertation thesis (though I worked with plants and not animals), and the fact that the other portion (diurnal or circadian rhythm) was the recipient of the 2017 Nobel Prize in Physiology or Medicine (and had been awarded to a trio of scientists–Dr. Jeffrey C. Hall, Dr. Michael Rosbash, and Dr. Michael W. Young).
The paper “A genome-wide microRNA screen identifies the microRNA-183/96/182 cluster as a modulator of circadian rhythms” and was published recently in the journal Proceedings of the National Academy of Science. While I haven’t read the paper, I am going to figure out a way to access it (without hopefully having to pay for it), or maybe wait for to to be freely accessible.
So, basically every living thing has a circadian clock (the internal 24-hour clock that is basically running on auto-pilot in the background carrying out the day-to-day essential functions of living).
Most research has been focused on the protein-protein interactions and various pathways and feedback loops. This group changed their focus and looked at a specific class of non-coding RNAs (miRNAs) that regulate genes, but at the transcriptional level.
They screened almost a thousand microRNAs in a luciferase reporter system that was engineered to glow on and off based on the cell’s specific 24-hr circadian clock.
To their surprise, they found 120 microRNAs that affected the bacteria’s circadian clock. Looking at the microRNAs, they decided to go with the cluster miR183/96/182, as mi96 showed to regulate PER2 (which is a core circadian clock gene).
They then went on to knocking out the cluster in the bacteria, and found that depending on how they knocked out the cluster (leaving one miRNA present), they either shortened the circadian period or increased the amplitude of the period.
Wanting to see how the cluster affected the circadian clock in mammals, they knocked the cluster out in mice and found that the mice lacking the cluster had a more difficult time trying to run on a wheel in the dark.
It will be interesting to see how miRNAs, the circadian clock, and disease all tie together.
The final article that I read this week was “Marine natural products identified with potential to treat lethal RNA viruses”.
The title of the actual research paper is “Natural products with the potential to treat RNA virus pathogens including SARS-CoV2” and was published in the Journal of Natural Products. This is a journal that if I renew my membership in the American Chemical Society I should be able to gain access to at some point this year.
So there is a big push in science to find natural products that can serve as antiviral, antibacterial, antifungal, antiparastic, and anticarcinogenic treatments. This is due in part to various things (such as bacteria and cancer cells) finding ways to get around current treatments.
There is already quite a bit of research going in this area in terms of looking at plants and soil bacteria (plus other soil organisms), for natural products. Recently there has been a push to look at the oceans for other potential natural products that could be beneficial to human health.
Currently there are ~21 pharmaceuticals that can trace their discovery to a marine natural product. For example, Marizomib (an potential proteasome inhibitor) is in clinical trials for be used as a potential treatment for different brain cancers.
It can trace its discovery to a genus of marine bacteria that was collected from seafloor sediments in 1990 by scientists at the Scripps Institute of Oceanography.
The scientists are looking to develop a library of compounds with medicinal potential from natural products found in the marine environment (so metabolites from various organisms).
The one thing that I found interesting was that I didn’t realize that members of only 3 RNA virus families have caused all the viral epidemics and pandemics throughout human history (or at least since we’ve started recording it). These 3 virus families (Coronaviridae, Flaviviridae, & Filoviridae) are responsible for the following viruses: SARS-CoV2 (COVID19), dengue fever, West Niles encephalitis, Zika, Ebola, and Marburg disease.
The thought that a treatment is just floating under the waves for any of these viral diseases is quite fascinating–as we are still learning what is actually living under the waves. But it also serves as a reminder that we need to continue (and improve) the protections we have in place for the oceans. These waters cover almost 70% of the planet, so it really shouldn’t be a surprise that the cure/remedy/treatment for numerous diseases caused by viruses could be under the waves.
So this wraps up my first science news round up. I realize that it is an extremely long post, and I may try to do it in two parts moving forward or just limit the number of articles I recap (here I did five articles).
I hope that this has been beneficial to you, and let me know if it still seems to have too much scientific jargon, which topic you found interesting, and also possibly what topic(s) you would like me to dive deeper into with either a series of blog posts or pages under the ‘all things science’ category.
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