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Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are two fatal and incurable neurodegenerative diseases linked by a shared genetic cause – a heterozygous hexanucleotide (GGGGCC) repeat expansion in a single allele of the C9orf72 gene. The goal of this work is to develop novel CRISPR based therapeutic gene editing technologies and test whether gene editing can reverse the cellular pathology caused by this repeat expansion in patient derived cells. The results of these studies will advance our use of CRISPR technologies for therapeutic editing in FTD/ALS, inform our understanding of the regulation of C9orf72 gene, and will be applicable to many other repeat expansion and single gene disorders.

Their findings, published in a Cell Reports paper titled “Palmitoylation and PDE6δ regulate membrane-compartment-specific substrate ubiquitylation and degradation,” have implications for developing new therapies.

Lead author Shafi Kuchay, assistant professor of biochemistry and in the College of Medicine and member of the University of Illinois Cancer Center at UIC, said that most common drugs work by targeting proteins that are located at the membranes of cells. Many of these proteins can cause diseases by being overly active. Unfortunately, most currently available drugs just block the activity of the harmful proteins, and while they are helpful in the short term, resistance to the drugs can develop over time.

University of Calgary researchers designed a novel imaging and experimental preparation system, allowing them to record the activity of the enteric nervous system in mice. The new technique allows researchers to record what is sometimes referred to as the gut’s brain during the complex processes of digestion and waste elimination.

“This completely different way of conducting experiments allows us to better understand the complexity of the nerve interactions that are regulating and coordinating the responses by the gut’s nervous system,” says Dr. Wallace MacNaughton, Ph.D., co-principal investigator. “It opens up new avenues for us to understand what’s really going on, and that’s going to help us understand and disorders a lot better.”

Neurons, or nerve cells, embedded in the wall of the gut precisely control its movements. The team used mice genetically encoded with fluorescent labels, so the neurons in the gut’s nervous system would “light up,” glowing green under microscopes, whenever the neurons were activated. The images are already providing new insights.

Are you ready to explore the future and imagine the incredible technological advancements that await us in the year 2090? From Neural Interfaces to Hypersonic Vactrains, Photosynthetic Humans, Fully Immersive Virtual Realities, Self-Healing Materials, and Genetic Enhancement, our world will look nothing like it does today.

Imagine controlling devices with your thoughts through Neural Interfaces, traveling from New York to Los Angeles in just 30 minutes with Hypersonic Vactrains, fueling your body with the sun with Photosynthetic Humans, immersing yourself in fully realistic virtual environments, repairing materials instantly with Self-Healing Materials, and enhancing your genetics for better physical and mental capabilities.

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The behavioral disorders observed in autism are associated with a multitude of genetic alterations. Scientists from the Hector Institute for Translational Brain Research (HITBR) have now found another molecular cause for this condition. The transcription factor MYT1L normally protects the molecular identity of nerve cells. If it is genetically switched off in human nerve cells or in mice, the functional changes and symptoms typical of autism occur. A drug that blocks sodium channels in the cell membrane can reverse the consequences of MYT1L failure and alleviate the functional and behavioral abnormalities in mice.

Disorders from the autism spectrum (ASD, autism spectrum disorders) are not only manifested by impairments in social interaction, communication, interest formation, and by stereotypical behavior patterns. This is often accompanied by other abnormalities such as epilepsy or hyperactivity.

Scientists are intensively searching for the molecular abnormalities that contribute to this complex developmental disorder. A multitude of genetic factors that influence the molecular programs of the nerve cells have already been linked to the development of autism.

A decades-old drug used to treat urinary tract infections (UTIs) appears to have saved the life of a man infected by the “brain-eating” amoeba — and his case highlights the tremendous potential of a new type of genetic sequencing technology.

The patient: In 2021, a 54-year-old man was admitted to a Northern California hospital following a seizure. After an MRI revealed a mass in his brain, he was transferred to the UCSF Medical Center, where the mass was biopsied.

Based on the biopsy, doctors suspected that the patient’s brain was being attacked by an amoeba — a highly dangerous and unusual infection. They sent a sample to the University of Washington, Seattle, where a PCR test identified the pathogen as Balamuthia mandrillaris — a deadly brain-eating amoeba that kills more than 90% of people it infects.

Scientists from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, have removed a major roadblock to better understanding of mpox (formerly, monkeypox). They developed a mouse model of the disease and used it to demonstrate clear differences in virulence among the major genetic groups (clades) of mpox virus (MPXV).

The research, appearing in Proceedings of the National Academy of Science, was led by Bernard Moss, M.D., Ph.D., chief of the Genetic Engineering Section of NIAID’s Laboratory of Viral Diseases.

Historically, mpox, a disease resembling smallpox, was only occasionally transmitted from rodents to non-human primates or people, and was observed primarily in several African countries. Mpox rarely spread from person to person. That pattern changed in 2022 with an outbreak in which person-to-person mpox transmission occurred in more than 100 locations worldwide.

One question for Brad Ringeisen, a chemist and executive director of the Innovative Genomics Institute. Founded by Nobel Prize-winning biochemist Jennifer Doudna, it aims to bridge revolutionary gene-editing tool development to affordable and accessible solutions in human health and climate.

Will CRISPR cure cancer?

We’re always thinking about: What are those targets in the future? Cancer is one of those things. The biggest impact is going to be what’s called systemic delivery, or in vivo delivery. There’s been one example of this in the community right now—to treat a liver disease. Intellia Therapeutics, a biotech company, has shown that you can actually intravenously apply CRISPR-Cas9 treatment. (CRISPR is the guide RNA, the targeting molecule, and Cas9 is the cutting molecule that edits DNA.) It can go to the liver and target the liver cells, and make edits at a high enough efficacy to treat genetic liver disease. The problem is that the liver is the easiest. It’s like the garbage can of the body. Pretty much anything that you put into the body is ultimately going to find its way to the liver. So that’s absolutely the easiest tissue to deliver to. But trying to deliver to a solid tumor, or to the brain, is much more difficult.

An artificial intelligence program may enable the first simple production of customizable proteins called zinc fingers to treat diseases by turning genes on and off.

The researchers at NYU Grossman School of Medicine and the University of Toronto who designed the tool say it promises to accelerate the development of gene therapies on a large scale.

Illnesses including cystic fibrosis, Tay-Sachs disease, and are caused by errors in the order of DNA letters that encode the operating instructions for every human cell. Scientists can in some cases correct these mistakes with gene editing methods that rearrange these letters.

An exploration of the structure of deoxyribonucleic acid, or DNA. If you want to learn more, join our free MITx #700x Introduction to Biology course (http://bit.ly/700xBio) or our #703x Genetics (https://bit.ly/GeneticsPart1) Also try #705x Biochemistry. (http://bit.ly/705xBiochem) or our advanced #728x Molecular Biology course (http://bit.ly/MITx7281x). Learn more about our work: http://web.mit.edu/mitxbio/courses.html.

This video was created for MITx 7.28.1x Molecular Biology: DNA Replication & Repair, offered on edX.

Created by Betsy Skrip (http://betsyskrip.com) and Sera Thornton (http://serathornton.com), with special thanks to Mary Ellen Wiltrout, Stephen Bell, Ceri Riley, and Julian Samal.

© 2015 Massachusetts Institute of Technology. All rights reserved.