Could humans ever regenerate a heart? A new study suggests the answer is 'yes'

When Mark Martindale decided to trace the evolutionary origin of muscle cells, like the ones that form our hearts, he looked in an unlikely place: the genes of animals without hearts or muscles.

In a new study published in the journal Proceedings of the National Academy of Sciences, the University of Florida scientist and colleagues found genes known to form hearts cells in humans and other animals in the gut of a muscle-less and heartless sea anemone. But the sea anemone isn't just any sea creature. It has superpower-like abilities: Cut it into many pieces and each piece will regenerate into a new animal.

So why does the sea anemone regenerate while humans cannot? When analyzing the function of its "heart genes," study researchers discovered a difference in the way these genes interact with one another, which may help explain its ability to regenerate, said Martindale, a UF biology professor and director of the Whitney Lab for Marine Bioscience in St. Augustine.

The study's findings point to potential for tweaking communication between human genes and advancing our ability to treat heart conditions and stimulate regenerative healing, he said.

"Our study shows that if we learn more about the logic of how genes that give rise to heart cells talk to each other, muscle regeneration in humans might be possible," Martindale said.

These heart genes generate what engineers calls lockdown loops in vertebrates and flies, which means that once the genes are turned on, they tell each other to stay on in an animal's cells for its entire lifetime. In other words, animals with a lockdown on their genes cannot grow new heart parts or use those cells for other functions.

"This ensures that heart cells always stay heart cells and cannot become any other type of cell," Martindale said.

But in sea anemone embryos, the lockdown loops do not exist. This finding suggests a mechanism for why the gut cells expressing heart genes in sea anemones can turn into other kinds of cells, such as those needed to regenerate damaged body parts, Martindale said.

The study supports the idea that definitive muscle cells found in the majority of animals arose from a bifunctional gut tissue that had both absorptive and contractile properties. And while the gut tissue of a sea anemone might not look like a beating heart, it does undergo slow, rhythmic peristaltic waves of contraction, much like the human digestive system.

Study authors argue that the first animal muscle cells might have been very heart-like, Martindale said.

"The idea is these genes have been around a long time and preceded the twitchy muscles that cover our skeleton," Martindale said.

Continued research could one day allow scientists to coax muscles cells into regenerating different kinds of new cells, including more heart cells, Martindale said

How bacteria survive antibiotic treatment

Multiresistant bacteria Scientists around the world are working hard to win the battle against multi-resistant bacteria. A new publication from the BASP Centre, University of Copenhagen now presents how even sensitive bacteria often manage to survive antibiotic treatment as so-called 'persister cells'. The comprehensive perspective on this phenomenon may help to improve current options of drug treatment and could even inspire the discovery of novel antibiotics targeting these notoriously difficult-to-treat persister bacteria.

In the current issue of the journal Science, Alexander Harms and colleagues from the BASP Centre, Department of Biology, University of Copenhagen summarise newly discovered molecular mechanisms explaining how bacteria manage to survive antibiotic treatment and cause chronic and recurrent infections.

Post-Doc Alexander Harms explains: "This amazing resilience is often due to hibernation in a physiological state called persistence where the bacteria are tolerant to multiple antibiotics and other stressors. Bacterial cells can switch into persistence by activating dedicated physiological programs that literally pull the plug of important cellular processes. Once they are persisters, the bacteria may sit through even long-lasting antibiotic therapy and can resuscitate to cause relapsing infections at any time after the treatment is abandoned."

Using novel detection methods, recent work in the field has uncovered the molecular architecture of several cellular pathways underlying the formation of bacterial persisters -- and these results confirmed the long-standing notion that persistence is intimately connected to slow growth or dormancy. Bacterial persistence can therefore be compared to hibernation of animals or the durable spores produced by many mushrooms and plants.

Across many different bacteria, these programs are controlled by a regulatory compound known as "magic spot" that plays a central role in the persistence phenomenon. These important discoveries, many of which were accomplished by the BASP Centre, may in the future facilitate the development of improved drug treatment regimens and eventually lead to the development of novel antibiotics.


Scientists show how mutation causes incurable premature aging disease

Scientists have demonstrated how a mutation in a specific protein in stem cells causes an incurable premature aging disease called dyskeratosis congenita, and were able to introduce the mutation into cultured human cells using gene editing technology.

The study findings provide a drug target for the disease, said lead study author Jayakrishnan Nandakumar, assistant professor of molecular, cellular and developmental biology at the University of Michigan.

The mutation compromises the function of an enzyme known as telomerase, which fuels stem cell division, he said. Stem cells must divide to repair old tissue.

This mutation, which occurs in the telomere protein TPP1, causes stem cells to slow or stop dividing in people with this rare, incurable disease. This can cause tissue breakdown, premature aging, bone marrow failure, cancer and even death.

Nandakumar and his U-M colleagues are believed to be the first to use genome editing technology called CRISPR/CAS9 to introduce a dyskeratosis congenita mutation into human cells.

This gene editing technology is often described as a pair of molecular scissors, because it cuts DNA in precise locations to allow for additions, deletions and replacements of DNA near the cut. The acronyms stand for Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated (CAS9).

The patient relevant to the study had one mutant gene, but also one normal TPP1 gene, yet still suffered from the disease. Nandakumar's group wanted to know if introducing one copy of the mutant TPP1 gene into cultured human cells using the CRISPR/CAS9 gene editing technology would compromise telomerase function in those cells, too.

It did, which meant that the mutation caused the disease.

"We envision that correcting the mutation in the stem cells of the patient will reverse the cellular symptoms of the disease, if and when such technology becomes available," Nandakumar said.

Understanding how the TPP1 mutation works also has implications for treating cancer patients, he said. This is because while the TPP1 mutation inhibits stem cell division in people with dyskeratosis congenita, normal TPP1 fuels cell division in people with cancer.

DNA is life's blueprint? No, master controller of the cell

ASK me what a genome is, and I, like many science writers, might mutter about it being the genetic blueprint of a living creature. But then I'll confess that "blueprint" is a lousy metaphor since it implies that the genome is two-dimensional, prescriptive and unresponsive.

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