Lifeboat Foundation

Gene therapies have the potential to treat neurological disorders like Alzheimer’s and Parkinson’s diseases, but they face a common barrier—the blood-brain barrier. Now, researchers at the University of Wisconsin-Madison have developed a way to move therapies across the brain’s protective membrane to deliver brain-wide therapy with a range of biological medications and treatments.

“There is no cure yet for many devastating brain disorders,” says Shaoqin “Sarah” Gong, UW-Madison professor of ophthalmology and visual sciences and biomedical engineering and researcher at the Wisconsin Institute for Discovery. “Innovative brain-targeted delivery strategies may change that by enabling noninvasive, safe and efficient delivery of CRISPR genome editors that could, in turn, lead to genome-editing therapies for these diseases.”

CRISPR is a molecular toolkit for editing genes (for example, to correct mutations that may cause disease), but the toolkit is only useful if it can get through security to the job site. The blood-brain barrier is a membrane that selectively controls access to the brain, screening out toxins and pathogens that may be present in the bloodstream. Unfortunately, the barrier bars some beneficial treatments, like certain vaccines and gene therapy packages, from reaching their targets because in lumps them in with hostile invaders.

Twenty years ago, following the initial sequencing of the human genome, geneticists started carrying out extensive genome-wide association studies to find genomic regions connected to human disease.

In addition to the DNA sequence, another stable level of molecular data created during development called epigenetic modifications also plays a role in disease risk.

Researchers have been examining these epigenetic changes for more than ten years to look for links to disease. More than a thousand of these epigenome-wide association studies have been published as of late.

Researchers look at DNA of lab mice and ultimately reverse ageing process Related: Empowered Aging Scientists have made a new discovery about how to reverse the ageing process through looking at the way in which cells in DNA are organised. In a new study published in Cell, David Sinclair, who is a professor of genetics at Harvard Medical School, and his team described how they looked at a genome, which is called epigenome, in mice to study the ageing process.

CRISPR/Cas9 technology-mediated genome editing has significantly improved the targeted inactivation of genes in vitro and in vivo in many organisms. In this study, we have reported a novel CRISPR-based vector system for conditional tissue-specific gene ablation in zebrafish. Specifically, the cardiac-specific cardiac myosins light chain 2 (cmlc2) promoter drives Cas9 expression to silence the neuropilin-1(nrp1) gene in cardiomyocytes in a heat-shock inducible manner. This vector system establishes a unique tool to regulate the gene knockout in both the developmental and adult stages and hence, widens the possibility of loss-of-function studies in zebrafish at different stages of development and adulthood. Using this approach, we investigated the role of neuropilin isoforms nrp1a and nrp1b in response to cardiac injury and regeneration in adult zebrafish hearts. We observed that both the isoforms (nrp1a and nrp1b) are upregulated after the cryoinjury. Interestingly, the nrp1b-knockout significantly altered heart regeneration and impaired cardiac function in the adult zebrafish, demonstrated by reduced heart rate (ECG), ejection fractions, and fractional shortening. In addition, we show that the knockdown of nrp1b but not nrp1a induces activation of the cardiac remodeling genes in response to cryoinjury. To our knowledge, this is the first study where we have reported a heat shock-mediated conditional knockdown of nrp1a and nrp1b isoforms using CRISPR/Cas9 technology in the cardiomyocyte in zebrafish, and furthermore have identified a crucial role for nrp1b isoform in zebrafish cardiac remodeling and eventually heart function in response to injury.

The authors have declared no competing interest.

Analyzing a person’s gene expression requires mapping their RNA landscape to a standard reference to gain insight into the degree to which genes are “turned on” and perform functions in the body. But researchers can run into issues when the reference does not provide enough information to allow for accurate mapping, an issue known as reference bias.

In a new paper published in the journal Nature Methods, researchers at UC Santa Cruz introduce the first-ever method for analyzing RNA sequencing data genome-wide using a “pantranscriptome,” which combines a transcriptome and a pangenome—a reference that contains genetic material from a cohort of diverse individuals, rather than just a single linear strand.

A group of scientists led by UCSC Associate Professor of Biomolecular Engineering Benedict Paten have released a toolkit that allows researchers to map an individual’s RNA data to a much richer reference, addressing reference bias and leading to much more accurate mapping.

Many genetic diseases are caused by diverse mutations spread across an entire gene, and designing genome editing approaches for each patient’s mutation would be impractical and costly.

Investigators at Massachusetts General Hospital (MGH) have recently developed an optimized method that improves the accuracy of inserting large DNA segments into a genome.

This approach could be used to insert a whole normal or “wild-type” replacement gene, which could act as a blanket therapy for a disease irrespective of a patient’s particular mutation.

Scientists continue to expand the technological frontiers of CRISPR, along with its enormous potential, in areas ranging from human health to global food supplies. Such is the case with CRISPR-based gene drives, a genetic editing tool designed to influence how genetic elements are passed from one generation to the next.

Gene drives designed for mosquitoes have the potential to curb the spread of malarial infections that cause hundreds of thousands of deaths each year, yet safety issues have been raised because such drives can spread quickly and dominate entire populations. Scientists have explored the principles governing the spread of gene-drive elements in targeted populations such as mosquitoes by testing many different combinations of components that constitute the drive apparatus. They have found, however, that there’s still more to explore and that key questions remain.

In the journal Nature Communications, University of California San Diego researchers led by former Postdoctoral Scholar Gerard Terradas, together with Postdoctoral Scholar Zhiqian Li and Professor Ethan Bier, in close collaboration with UC Berkeley graduate student Jared Bennett and Associate Professor John Marshall, describe the development of a new system for testing and developing gene drives in the laboratory and safely converting them into tools for potential real-world applications.

Scientists have developed a wireless, battery-free implant capable of monitoring dopamine signals in the brain in real-time in small animal models, an advance that could aid in understanding the role neurochemicals play in neurological disorders.

The device, detailed in a study published in ACS Nano, activates or inhibits specific neurons in the brain using light, a technique known as optogenetic stimulation. It also records dopamine activity in freely behaving subjects without the need for bulky or prohibitive sensing equipment, said John Rogers, Ph.D., the Louis Simpson and Kimberly Querrey Professor of Materials Science and Engineering, Biomedical Engineering and Neurological Surgery, and a co-author of the study.

“This device allows neuroscientists to monitor and modulate brain activity in real-time and in a programmable fashion, in mice—a very important class of animal model for neuroscience studies,” Rogers said.

In this video I showcase a program that I have been working on for simulating evolution by natural selection. I dive into various mechanisms of the simulation and go over some interesting real-life biology in the process. The key aim of this project is to evolve multicellular organisms, starting from single-celled protozoa-like creatures that must collect mass and energy from their surroundings in order to survive, grow and reproduce.

Chapters:
00:00 — Introduction.
00:56 — Life of a protozoan.
02:46 — The start of the simulation.
05:57 — How the cells work.
06:53 — Introducing multicellular colonies.
08:33 — Understanding evolution.
11:38 — Looking at data from the simulation.
13:27 — Evolving epigenetics introduction.
14:14 — Waddington’s Landscape and cell specialisation.
15:22 — The Central Dogma of Molecular Biology.
16:05 — Gene Regulatory Networks.
16:54 — Outro.
17:30 — Watching the simulation.

Continue reading “Simulating Cellular Evolution: The Path To Multicellularity” »