Toggle light / dark theme

Integrated structural biology provides new clues for cystic fibrosis treatment

Scientists at St. Jude Children’s Research Hospital and Rockefeller University have combined their expertise to gain a better understanding of the cystic fibrosis transmembrane conductance regulator (CFTR). Mutations in CFTR cause cystic fibrosis, a fatal disease with no cure.

Current therapies using a drug called a potentiator can enhance CFTR functions in some patients; but how the potentiators work is not well understood. The new findings reveal how CFTR functions mechanistically and how disease mutations and potentiators affect those functions. With this information, researchers may be able to design more effective therapies for cystic fibrosis. The study was published today in Nature.

Cystic fibrosis is a genetic disorder that causes people to produce mucus that is too thick and sticky. This can block airways and lead to lung damage as well as cause problems with digestion. The disease affects about 35,000 people in the United States. CFTR is an anion channel, a passageway that maintains the right balance of salts and fluid across epithelial and other membranes. Mutations in CFTR are what cause cystic fibrosis, but these mutations can affect CFTR function differently. Therefore, some drugs used to treat the disease can only partially restore function of specific mutant forms of CFTR.

Blood Test #2 in 2023: Diet Composition

Join us on Patreon! https://www.patreon.com/MichaelLustgartenPhD

Discount Links:
NAD+ Quantification: https://www.jinfiniti.com/intracellular-nad-test/
Use Code: ConquerAging At Checkout.

Green Tea: https://www.ochaandco.com/?ref=conqueraging.

Oral Microbiome: https://www.bristlehealth.com/?ref=michaellustgarten.

Epigenetic Testing: https://bit.ly/3Rken0n.
Use Code: CONQUERAGING!

At-Home Blood Testing: https://getquantify.io/mlustgarten.

Writing the Rules on CRISPR Activation

The researchers add that these data demonstrate that CRISPRa is generally applicable across chromatin states and cell types, and highlights the factors that impact the degree of gene activation and how easy it is to reproduce the effects. Understanding these factors is important in the design and analysis of CRISPRa screens, which are used to look for genes involved in genetic diseases, the team points out.

Further study is required to continue to add to these rules and to see whether different CRISPRa or CRISPR interference techniques behave in a similar way.

“Our research has established a system for reporting the effectiveness of CRISPR activation in stem cells, allowing us to gain a better understanding of how CRISPRa works in multiple cell states,” says Qianxin Wu, PhD, first author from Wellcome Sanger. “We also showed that CRISPR gene activation is powerful enough to induce stem cells to differentiate into other cell states. This suggests that CRISPRa screens can be used to search for genes involved in cellular processes or to generate more accurate models of cell types in the body, aiding research into genetic diseases and regenerative medicine.”

Important step towards accurate use of stem cell–based disease models

Induced pluripotent stem cells offer great therapeutic potential and are a valuable tool for understanding how different diseases develop. New research shows that such stem cell lines should be regularly screened for genetic mutations to ensure the accuracy of the disease models.

In the past 10 years, scientists have learned to create induced (iPSC) from ordinary cells by genetic reprogramming. These cells are widely used to study diseases, as they can be differentiated to almost any cell type of the body, and they can be generated from any individual. However, a key remaining methodological challenge is that the differentiation process is subject to major technical variation for mostly unknown reasons.

HiLIFE Tenure Track Professor Helena Kilpinen and her group at the University of Helsinki use for studying the biological mechanisms of neurodevelopmental and other brain-related diseases.

Michael Levin: Epigenetic Adaptation, Bioelectricity, Anatomical Compiler — Learning with Lowell 170

Michael Levin is a biologist at Tufts University working on novel ways to understand and control complex pattern formation in biological systems.

Michael Levin links.
Michael’s Twitter: https://twitter.com/drmichaellevin.
Michael’s Website: https://drmichaellevin.org.

PODCAST INFO:
The Learning With Lowell show is a series for the everyday mammal. In this show we’ll learn about leadership, science, and people building their change into the world. The goal is to dig deeply into people who most of us wouldn’t normally ever get to hear. The Host of the show – Lowell Thompson-is a lifelong autodidact, serial problem solver, and founder of startups.

LINKS
Youtube: https://www.youtube.com/channel/UCzri06unR-lMXbl6sqWP_-Q
Youtube clips: https://www.youtube.com/channel/UC-B5x371AzTGgK-_q3U_KfA
Linkedin: https://www.linkedin.com/in/lowell-thompson-2227b074
Twitter: https://twitter.com/LWThompson5
Website: https://www.learningwithlowell.com/

Shownotes/ Timestamps.
00:00 Introducing Michael Levin.
00:30 Epigenetic Head Exploding adaptation Planaria.
05:45 Generalize vs intelligent search epigenetic adaptation.
08:55 Designing studies to test these hypothesis.
12:35 Implications of hypothesis proven out.
19:40 Mitochondria domestication hypothesis.
25:50 Where are memories stored if not the brain.
34:45 Regeneration of memories evidence.
38:00 Voltage on both sides of amputated limb, and what catalyzes regeneration.
42:55 Induce physiology of extinct species from live species.
47:55 Biomanufacturing.
55:30 Anatomical compiler development.
57:45 Horse vs zebra domestication.
59:20 Bioelectricity resurrection.
01:02:05 Regeneration vs Brain computer interface for restoring function.
01:06:50 What is needed to achieve his vision for regeneration, bioelectricity, etc.
01:08:42 Structure needed to support development.
01:11:03 Groups coming together.
01:12:25 Longevity & health span — high level vs low level approach.
01:14:45 Cancer — why mortal cell become an immortal cell.
01:19:20 Advice for 25–35 year olds.
01:22:46 Age he discovered life goal.
01:23:55 How old he feels mentally.
01:24:55 Books.
01:25:55 Working to learn currently.

#Bioelectricity #MichaelLevin #Regeneration

Gene therapy: Everything you need to know about the DNA-tweaking treatments

Gene therapy has been headline news in recent years, in part due to the rapid development of biotechnology that enables doctors to administer such treatments. Broadly, gene therapies are techniques used to treat or prevent disease by tweaking the content or expression of cells’ DNA, often by replacing faulty genes with functional ones.

The term “gene therapy” sometimes appears alongside misinformation about mRNA vaccines, which include the Pfizer and Moderna COVID-19 vaccines. These vaccines contain mRNA, a genetic cousin of DNA, that prompts cells to make the coronavirus “spike protein.” The vaccines don’t alter cells’ DNA, and after making the spike, cells break down most of the mRNA. Other COVID-19 shots include the viral vector vaccines made by AstraZeneca and Johnson & Johnson, which deliver DNA into cells to make them build spike proteins. The cells that make spike proteins, using instructions from either mRNA or viral vector vaccines, serve as target practice for the immune system, so they don’t stick around long. That’s very, very different from gene therapy, which aims to change cells’ function for the long-term.

Cryo-electron microscopy captures structure of a protein pump

Hailey-Hailey disease is a rare, inherited condition characterized by patches of blisters appearing mainly in the skin folds of the arm pits, groin and under the breasts. It is caused by a mutation in the gene that codes for a specific protein involved in the transportation of calcium and manganese ions from the cell cytoplasm and into a sac-like organelle called the Golgi apparatus.

Scientists at Tohoku University, together with colleagues in Japan, have uncovered some aspects of this ’s structure that could help researchers understand how it works. The findings, published in the journal Science Advances, help build the foundations for research into finding treatments for Hailey-Hailey disease and other neurodegenerative conditions.

The protein the team studied is called secretory pathway Ca2+/Mn2+-ATPase, or SPCA for short. It is located in the Golgi apparatus, a cellular sac-like structure that plays a crucial role in protein quality control before they are released into cells. The Golgi apparatus also acts like a sort of calcium ion storage container. Calcium ions are vital for cell signaling processes and are important for proteins to function properly, so maintaining the right calcium ion balance inside cells is necessary for their day-to-day activities.

The Rise Of Genetic Engineering | Gene-Editing | Documentary

Genetic Engineering extends far beyond the controversial news headlines that obsess over ‘designer babies’. In the science community, gene-editing tools like CRISPR and PRIME editing will do nothing less than save the planet.

The Rise Of Genetic Engineering (2022)
Writers: Kyle McCabe, Christopher Webb Young.
Stars: Rodolphe Barrangou, George Church, Mary Beth Dallas.
Genre: Documentary.
Country: United States.
Language: English.
Release Date: August 24, 2022 (United States)

Synopsis:
Genetic Engineering extends far beyond the controversial news headlines that obsess over ‘designer babies’. In the science community, gene-editing tools like CRISPR and PRIME editing will do nothing less than save the planet.

Methods like this allow scientists to alter and ‘re-program’ the genetics of living organisms.

This episode shows scientists at large using gene-editing technologies to revolutionize the food supply chain, bolstering food crops to prevent famines, and even speed up reforestation efforts that will reverse global warming. Genetic Engineering in farm animals is helping scientists to ‘select’ desirable traits, like physical features and gender. Incredibly, one scientist is using gene-editing technologies to resurrect the DNA of extinct species, like the Wooly Mammoth!

Despite some public concern, gene-editing is definitely a cause for hope in the fight against genetic disorders in humans. It’s already reversing a type of congenital blindness in children. And with the hyper-precision afforded by PRIME editing being prepared for clinical trials, a much more hopeful world will be revealed for families in the future.

The Hidden Genes That Make Us Human

Check out Brilliant here: https://brilliant.org/Eons.

In the search for the genes that make us human, some of the most important answers were hiding not in the genes themselves, but in what was once considered genomic junk.

Thanks to Riley J. Mangan, Ph.D. Candidate, Molecular Genetics and Microbiology, Duke University for his help with this episode!

*
PBS Member Stations rely on viewers like you. To support your local station, go to http://to.pbs.org/DonateEons.
*

Produced by complexly for PBS digital studios.

Super special thanks to the following Patreon patrons for helping make Eons possible:

Researchers detail groundbreaking Angelman syndrome development

Researchers at Texas A&M University have developed the first molecular therapeutic for Angelman syndrome to advance into clinical development.

In a new article, published today in Science Translational Medicine, Dr. Scott Dindot, an associate professor and EDGES Fellow in the Texas A&M School of Veterinary Medicine and Biomedical Sciences’ (VMBS) Department of Veterinary Pathobiology, and his team share the process through which they developed this novel therapeutic candidate, also known as 4.4.PS.L, or GTX-102. Dindot is also the executive director of molecular genetics at Ultragenyx, which is leading the development of GTX-102.

Angelman syndrome (AS) is a devastating, rare neurogenetic disorder that affects approximately 1 in 15,000 per year; the disorder is triggered by a loss of function of the maternal UBE3A gene in the brain, causing , absent speech, movement or balance disorder, and seizures.