#38 Heart Failure, Plastic Problems and Hibernating to Stay Younger?
New insight into the cellular biology of human heart failure, engineering enzymes to help solve the global plastic crisis and hibernating slows ageing in bats...
🫀Human Heart Failure
New insight into the cellular biology of human heart failure…
Researchers have provided new insights into the cellular and molecular biology of human hearts. This has been done through the studying of both heart samples from patients with cardiomyopathies as well as a control group.
Human heart failure is a highly fatal condition that affects over 20 million people across the world. Heart failure occurs when the heart is unable to pump blood around the body properly. The new breakthrough utilises single nucleus RNA sequencing (snRNAseq) analysis. The study’s author said that this analysis "upends a prevalent dogma that heart failure results from a common final pathway, and can guide the future development of therapies with selective targets to enhance personalized medicine."
Cardiomyopathy is a group of diseases that affect the heart muscle in ways that interfere with the organs ability to effectively pump blood. This serious disorder is one of the major causes of heart failure. Often cardiomyopathy’s are caused by genetic mutations that encode proteins holding diverse functions in cardiac biology.
However, exactly how the pathogenic variants in genes that are associated with dilate cardiomyopathy (DCM) and arrhythmogenic cardiopathy (ACM), convey such high risks, is unknown. While the idea that diverse stimuli converge on a common final pathway to lead to heart failure has been greater understood, new technologies provide direct opportunities to evaluate whether, instead, genotype influences disease pathway.
Daniel Reichart and colleagues performed the snRNAseq technique in heart tissue samples from the patients with genetic idiopathic (mutation negative) DCM and ACM as well as in those without structural heart disease. Through machine learning, the 880,000 transcriptomes the analysis generated, allowed the team to identify distinct cell types involved in the path towards heart failure and their locations in the heart.
The team said that "This network showed remarkably high prediction of the genotypes for each cardiac sample, thereby reinforcing our conclusion that genotypes activate very specific heart failure pathways," said the authors. "Although interrogation of these datasets provides ongoing opportunities for discovery, our findings provided substantial evidence that genotype influenced pathological remodelling of the heart."
🧋Solving Plastic Problem
Engineering enzymes to help solve the planet’s plastic problem…
A research team from the Manchester Institute of Biotechnology (MIB) have developed a new enzyme engineering platform to try and improve the efficiency and effectivity of plastic degrading enzymes. The team has engineered an enzyme that can successfully degrade poly(ethylene) terephthalate (PET), the plastic commonly used in plastic bottles to demonstrate their work and success.
Enzymatic recycling of plastic is seen as quite an attractive and environmentally friendly strategy to help alleviate the problems associated with plastic waste. Furthermore, there are a lot of existing methods for recycling that are far more cost inefficient for recycling plastics. Enzymes are arguably a more cost and energy efficient alternative. They are also capable of breaking down just specific components of mixed plastic waste streams that are currently difficult to use other technologies for.
Whilst they may seem a great option, there are still plenty of barriers that need to be overcome. One example being that natural enzymes ability to break down plastics typically are less effective and are unstable under the conditions needed for a industrial scale process.
Lead experimental worker, Dr Elizabeth Bell said that "The accumulation of plastic in the environment is a major global challenge. For this reason, we were keen to use our enzyme evolution capabilities to enhance the properties of plastic degrading enzymes to help alleviate some of these problems. We are hopeful that in the future our scalable platform will allow us to quickly develop new and specific enzymes are suitable for use in large-scale plastic recycling processes."
To test their platform and development, they went on to develop a new enzyme. HotPETase, was made through directed evolution of IsPETase. IsPETase is a recently discovered enzyme produced by the bacterium Ideonella sakaiensis, which can use PET as a carbon and energy source. Whilst IsPETase had the natural ability to degrade some semi-crystalline forms of PET, the enzyme was unstable at temperatures above 40C degrees. The low stability meant that the reactions must be run at temperatures below the glass transition temperature of Pet which leads to lower depolymerisation rates.
The team then devloped a thermostable enzyme to over come this. HotPETase, which is active at 70C degrees. This is above the glass transition temperature of PET. This enzyme can depolymerise semi-crystalline PET more rapidly than previously reported enzymes.
Professor Anthony Green, Lecturer in Organic Chemistry, said: "The development of HotPETase nicely illustrates the capabilities of our enzyme engineering platform. We are now excited to work with process engineers and polymer scientists to test our enzyme in real world applications. Moving forward, we are hopeful that our platform will prove useful for developing more efficient, stable, and selective enzymes for recycling a wide range of plastic materials."
The development of robust plastic degrading enzymes such as HotPETase, along with the availability of a versatile enzyme engineering platform, makes an important contributions towards the development of a biotechnological solution to the plastic waste problem.
🦇Hibernate = Staying Younger?
Hibernation slows biological ageing in bats…
The Big Brown Bat is the most common bat in the US. This species holds an unusually long lifespan of up to 19 years. A University of Maryland study identifies one of the secrets to this; hibernation.
UMD Biology Professor and the study’s senior author, Gerald Wilkinson said that "Hibernation has allowed bats, and presumably other animals, to stay in northerly or very southerly regions where there's no food in the winter,". He went on to say that "Hibernators tend to live much longer than migrators. We knew that, but we didn't know if we would detect changes in epigenetic age due to hibernation."
The research team determined that hibernating over one winter extends a big brown bat’s epigenetic clock, this being a biological marker of ageing, by 3/4 of a year.
The team analysed smaller tissue samples that were taken from the wings of 20 individual big brown bats (Eptesicus fuscus) during two periods. In the winter when they hibernated as well as when they were active in the summer.
Once the samples were collected the team measured the changed in DNA methylation, a biological process associated with gene regulation, between the two sample times. The key discovery was that DNA methylation occurred at certain sites in the bat’s genome, and that these sites appeared to be affecting metabolism during hibernation.
"It's pretty clear that the sites that decrease methylation in the winter are the ones that appear to be having an active effect," Wilkinson said. "Many of the genes that are nearest to them are known to be involved in regulating metabolism, so they presumably keep metabolism down."
Some of the genes are the same as ones that Wilkinson and fellow researchers identified as “longevity genes” in a previous study. Wilkinson said that “there is significant overlap between the hibernation genes and the longevity genes, further highlighting the link between hibernation and longer lifespans.”
The earlier study benefited this study in a few ways. One being that it established the first epigenetic clock for bats, capable of accurately predicting the age of any bat in the wild. The clock enabled this study to demonstrate that hibernation reduces a bat’s epigenetic age in comparison to a non-hibernating animal of the same age.
Wilkinson said that he is planning a follow-up study to compare epigenetic aging in big brown bats in Canada, where they hibernate, with the same species in Florida.
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🐼 Conservation
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😷 COVID
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🧪 Biochemistry
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🔬 Evolution
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🧬 Genetics
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📷 Weekly Camera Roll
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Reference List
Content may be adapted and edited for style and length.
🫀Human Heart Failure
Reichart, D., Lindberg, E., Maatz, H., Miranda, A., Viveiros, A., Shvetsov, N., Gärtner, A., Nadelmann, E., Lee, M., Kanemaru, K., Ruiz-Orera, J., Strohmenger, V., DeLaughter, D., Patone, G., Zhang, H., Woehler, A., Lippert, C., Kim, Y., Adami, E., Gorham, J., Barnett, S., Brown, K., Buchan, R., Chowdhury, R., Constantinou, C., Cranley, J., Felkin, L., Fox, H., Ghauri, A., Gummert, J., Kanda, M., Li, R., Mach, L., McDonough, B., Samari, S., Shahriaran, F., Yapp, C., Stanasiuk, C., Theotokis, P., Theis, F., van den Bogaerdt, A., Wakimoto, H., Ware, J., Worth, C., Barton, P., Lee, Y., Teichmann, S., Milting, H., Noseda, M., Oudit, G., Heinig, M., Seidman, J., Hubner, N. and Seidman, C., 2022. Pathogenic variants damage cell composition and single cell transcription in cardiomyopathies. Science, 377(6606).
🧋Solving Plastic Problem
Bell, E., Smithson, R., Kilbride, S., Foster, J., Hardy, F., Ramachandran, S., Tedstone, A., Haigh, S., Garforth, A., Day, P., Levy, C., Shaver, M. and Green, A., 2022. Directed evolution of an efficient and thermostable PET depolymerase. Nature Catalysis,.
🦇Hibernate = Staying Younger?
Sullivan, I., Adams, D., Greville, L., Faure, P. and Wilkinson, G., 2022. Big brown bats experience slower epigenetic ageing during hibernation. Proceedings of the Royal Society B: Biological Sciences, 289(1980).