Lifeboat Foundation

Small but mighty, lysosomes play a surprisingly important role in cells despite their diminutive size. Making up only 1–3% of the cell by volume, these small sacs are the cell’s recycling centers, home to enzymes that break down unneeded molecules into small pieces that can then be reassembled to form new ones. Lysosomal dysfunction can lead to a variety of neurodegenerative or other diseases, but without ways to better study the inner contents of lysosomes, the exact molecules involved in diseases—and therefore new drugs to target them—remain elusive.

A new method, reported in Nature on Sept. 21, allows scientists to determine all the molecules present in the lysosomes of any cell in mice. Studying the contents of these molecular recycling centers could help researchers learn how the improper degradation of cellular materials leads to certain diseases. Led by Stanford University’s Monther Abu-Remaileh, institute scholar at Sarafan ChEM-H, the study’s team also learned more about the cause for a currently untreatable neurodegenerative disease known as Batten disease, information that could lead to new therapies.

“Lysosomes are fascinating both fundamentally and clinically: they supply the rest of the cell with nutrients, but we don’t always know how and when they supply them, and they are the places where many diseases, especially those that affect the brain, start,” said Abu-Remaileh, who is an assistant professor of chemical engineering and of genetics.

For the memory prosthetic, the team focused on two specific regions: CA1 and CA3, which form a highly interconnected neural circuit. Decades of work in rodents, primates, and humans have pointed to this neural highway as the crux for encoding memories.

The team members, led by Drs. Dong Song from the University of Southern California and Robert Hampson at Wake Forest School of Medicine, are no strangers to memory prosthetics. With “memory bioengineer” Dr. Theodore Berger—who’s worked on hijacking the CA3-CA1 circuit for memory improvement for over three decades—the dream team had their first success in humans in 2015.

The central idea is simple: replicate the hippocampus’ signals with a digital replace ment. It’s no easy task. Unlike computer circuits, neural circuits are non-linear. This means that signals are often extremely noisy and overlap in time, which bolsters—or inhibits—neural signals. As Berger said at the time: “It’s a chaotic black box.”

The genetic encoding of ncAAs with distinct chemical, biological, and physical properties requires the engineering of bioorthogonal translational machinery, consisting of an evolved aminoacyl-tRNA synthetase/tRNA pair and a “blank” codon. To achieve this, the researchers mimicked the ibis’ ability to synthesize sTyr and incorporate it into proteins.

The Xiao lab employed a mutant amber stop codon to encode the desired sulfotransferase, resulting in a completely autonomous mammalian cell line capable of biosynthesizing sTyr and incorporating it with great precision into proteins.

These engineered cells, the authors wrote, can produce “site-specifically sulfated proteins at a higher yield than cells fed exogenously with the highest level of sTyr reported in the literature.” They used the cells to prepare highly potent thrombin inhibitors with site-specific sulfation.

https://youtube.com/watch?v=86YLFOog4GM

Can you believe that we have a state-of-the-art laboratory in space?

The International Space Station has been in low Earth orbit since 1998. Astronauts started to use the station in November 2000, when a module that provided a long-term life support and control system was added to the first two modules.

Continue reading “5 facts about the ISS that reveal why it is a masterpiece of engineering” »

A synthetic system that reproduces several attributes of living cells.

Intellia Therapeutics said Friday the first six patients to receive its CRISPR-based treatment for a genetic swelling disorder have safely had small, corrective changes made to dysfunctional DNA inside their liver cells.

Preliminary results from the study — just the second to show that CRISPR-based gene editing can be delivered systemically and performed in vivo, or inside the body — found that the treatment, NTLA-2002, reduced levels of the disease-causing protein, kallikrein, by 65% and 92% in the low-and high-dose cohort, respectively. In the low-dose group, the one-time infusion also reduced by 91% the painful swelling “attacks” commonly experienced by patients with a rare condition called hereditary angioedema, or HAE. Participants in the high-dose group have not yet completed the 16-week observation period.

Chardan hosted its 4th Annual Chardan Genetic Medicines Conference in October 2020, featuring over 80 public and private companies representing in vivo gene therapy, ex vivo gene therapy, gene editing, RNA medicines, and other subsegments of the genetic medicines space. Among our various panels with preeminent thought leaders, we spoke with newly-minted Nobel laureate, President of the Innovative Genomics Institute, and Professor of Molecular and Cell Biology and Chemistry at UC Berkeley, Jennifer Doudna.

PhD about open questions and areas of innovation in the CRISPR gene editing space.

In nature, evolutionary chromosomal changes may take a million years, but scientists have recently reported a novel technique for programmable chromosome fusion that has successfully created mice with genetic changes that occur on a million-year evolutionary scale in the laboratory. The findings might shed light on how chromosomal rearrangements – the neat bundles of structured genes provided in equal numbers by each parent, which align and trade or mix characteristics to produce offspring – impact evolution.

In a study published in the journal Science, the researchers show that chromosome level engineering is possible in mammals. They successfully created a laboratory house mouse with a novel and sustainable karyotype, offering crucial insight into how chromosome rearrangements may influence evolution.

“The laboratory house mouse has maintained a standard 40-chromosome karyotype — or the full picture of an organism’s chromosomes — after more than 100 years of artificial breeding,” said co-first author Li Zhikun, researcher in the Chinese Academy of Sciences (CAS) Institute of Zoology and the State Key Laboratory of Stem Cell and Reproductive Biology. “Over longer time scales, however, karyotype changes caused by chromosome rearrangements are common. Rodents have 3.2 to 3.5 rearrangements per million years, whereas primates have 1.6.”

These unnecessary experiments can cause another pandemic.

CRISPR has been used to rearrange the chromosomes of lab mice, a world’s first in mammals and a breakthrough in bioengineering.