Lifeboat Foundation: Safeguarding Humanity
Toggle light / dark theme

Blog

Category: biotech/medical – Page 878

Year 2022 😗

Automation is not just for high-throughput screening anymore. New devices and greater flexibility are transforming what’s possible throughout drug discovery and development. This article was written by Thomas Albanetti, AstraZeneca; Ryan Bernhardt, Biosero; Andrew Smith, AstraZeneca and Kevin Stewart, AstraZeneca for a 28-page DDW eBook, sponsored by Bio-Rad. Download the full eBook here.

A utomation has been a part of the drug discovery industry for decades. The earliest iterations of these systems were used in large pharmaceutical companies for high-throughput screening (HTS) experiments. HTS enabled the testing of libraries of small molecule compounds by a single or a series of multiple experimental conditions to i dentify the potential of those compounds as a treatment for a target disease. HTS has evolved to enable screening libraries of millions of compounds, but the high cost of equipment has largely resulted in automation occurring primarily in large pharmaceutical companies. Today, though, new types of robots paired with sophisticated software tools have helped to democratise access to automation, making it possible for pharma and biotechnology companies of almost any size to deploy these solutions in their labs.

Originally, automated solutions were only implemented for projects that involved a lot of repetitive tasks, which is typical of high-throughput experiments and assays. The equipment used in early automation efforts was expensive, specialised, and physically integrated together, effectively making the equipment unavailable for any non-automated use. Now, both the approaches and equipment are far more adaptive and flexible. The latest automation software is also much simpler to program, making it easier to swap in different instruments and robots as needed. For example, labs can run a particular HTS assay for a few weeks and then quickly pivot to run a new assay. Labs can also create and run bespoke standard operating procedures, assays, and experiments for drug targets they are interested in pursuing.

Continue reading “The rise of automation in drug discovery” | >

While “protein” often evokes pictures of chicken breasts, these molecules are more similar to an intricate Lego puzzle. Building a protein starts with a string of amino acids—think a myriad of Christmas lights on a string— which then fold into 3D structures (like rumpling them up for storage).

DeepMind and Baker both made waves when they each developed algorithms to predict the structure of any protein based on their amino acid sequence. It was no simple endeavor; the predictions were mapped at the atomic level.

Designing new proteins raises the complexity to another level. This year Baker’s lab took a stab at it, with one effort using good old screening techniques and another relying on deep learning hallucinations. Both algorithms are extremely powerful for demystifying natural proteins and generating new ones, but they were hard to scale up.

Read more | >

Clustered regularly interspaced short palindromic repeats (CRISPR)-associated Cas9 protein is an effector that plays a major role in a prokaryotic adaptive immune system, by which invading DNA can be targeted and cut for inactivation. The Cas9 endonuclease is directed to target sites by a guide RNA (gRNA) where Cas9 can recognize specific sequences (PAMs) in foreign DNA, which then serve as an anchoring point for cleavage of the adjacent RNA-matching DNA region. Although the CRISPR-Cas9 system has been widely studied and repurposed for diverse applications (notably, genome editing), its origin and evolution remain to be elucidated. Here, we investigate the evolution of Cas9 from resurrected ancient nucleases (anCas) in extinct firmicutes species as old as 2,600 myr to the current day. Surprisingly, we demonstrate that these ancient forms were much more flexible in their PAM and gRNA scaffold requirements compared to modern day Cas9 enzymes. In addition, anCas portrays a gradual paleoenzymatic adaptation from nickase to double-strand break activity, suggesting a mechanism by which ancient CRISPR systems could propagate when harboring Cas enzymes with minimal PAMs. The oldest anCas also exhibit high levels of activity with ssDNA and ssRNA targets, resembling Cas nucleases in related system types. Finally, we illustrate editing activity of the anCas enzymes in human cells. The prediction and characterization of anCas proteins uncovers an unexpected evolutionary trajectory leading to ancient enzymes with extraordinary properties.

R. P-J., B. A-L. are co-inventors on patent application filed by CIC nanoGUNE and licenced to Integra Therapeutics S.L. relating to work in this article. A. S-M. and M.G. are co-founders of Integra Therapeutics S.L. B.P.K is an inventor on patents and/or patent applications filed by Mass General Brigham that describe genome engineering technologies. B.P.K. is a consultant for Avectas Inc., EcoR1 capital, and ElevateBio, and is an advisor to Acrigen Biosciences and Life Edit Therapeutics.

Read more | >

When it comes to longevity in the animal kingdom, the Naked mole-rat is often touted as one of the longest living animals known to man, and some say that they functionally do not age, only ever dying of disease or predation. In this article we will investigate these claims, and discover what exactly is so exciting about these aesthetically challenged rodents which has made so many researchers so optimistic about the future of human longevity.

Are Naked Mole-Rats Immortal?

Let’s dispel one of the largest misconceptions about naked mole-rats (Heterocephalus glaber) before we dive into what makes these rodents so interesting. No, naked mole-rats are not immortal in any sense of the word. First documented in 1,842 by German naturalist Eduard RĂŒppell, we have formally studied this species of rodent for over 180 years, and we have yet to see any immortal naked-mole rats running around, in the wild or otherwise. Neither have we seen a naked mole-rat coming close to the longevity enjoyed by our own species, let alone the longevity enjoyed by other longer lived species such as the giant tortoise. However, it is not the lifespan itself that is so remarkable about the naked mole-rat, but rather its relative longevity compared to other rodents that makes the naked mole-rat so interesting.

Read more | >

For the first time, a new study has identified enlarged perivascular spaces in the brains of migraine sufferers. Results of the study were presented recently at the annual meeting of the Radiological Society of North America (RSNA).

“In people with chronic migraine and episodic migraine without aura, there are significant changes in the perivascular spaces of a brain region called the centrum semiovale,” said study co-author Wilson Xu, an M.D. candidate at Keck School of Medicine of the University of Southern California in Los Angeles. “These changes have never been reported before.”

Migraine is a common, often debilitating condition, involving a severe recurring headache. Migraines may also cause nausea, weakness, and light sensitivity. According to the American Migraine Foundation, over 37 million people in the U.S. are affected by migraine, and up to 148 million people worldwide suffer from chronic migraine.

Read more | >

The proteins can record histories of cellular events.

Researchers from MIT developed a technique to induce cells to record the history of cellular events in a long protein chain that can be imaged using a light microscope. The technique could help understand the critical steps involved in the processes, such as memory formation, response to drug treatment, and gene expression.

Studying the molecular processes within cells can provide important insights into their function and how they contribute to the overall functioning of an organ.

Design Cells/iStock.

Continue reading “MIT researchers developed self-assembling proteins that can store ‘cellular memories’” | >

“Proper hydration may slow down aging and prolong a disease-free life.”

It is an indisputable fact that drinking water is beneficial for our health. In addition to its contribution to metabolism, it also plays an important role in keeping the skin moist. According to the National Institutes of Health’s (NIH) new study, drinking water also links people to age in a healthy way.

As stated in the release, researchers looked at the relationship between several health markers and blood salt levels, which rise when fluid intake declines. The study included health information acquired from 11,255 participants over a 30-year period.

Rawpixel/iStock.

Continue reading “Scientists have revealed a link between drinking enough water and aging” | >

The first fully complete human genome with no gaps is now available to view for scientists and the public, marking a huge moment for human genetics. Announced in a preprint in June 2021, six papers have now been published in the journal Science. They describe the painstaking work that goes into sequencing an over 6 billion base pair genome, with 200 million added in this new research. The new genome now adds 99 genes likely to code for proteins and 2,000 candidate genes that were previously unknown.

Many will be asking: “wait, didn’t we already sequence the human genome?” In part, yes – in 2000, the Human Genome Sequencing Consortium published their first drafts of the human genome, results that subsequently paved the way for almost every facet of human genetics available today.

The most recent draft of the human genome has been used as a reference since 2013. But weighed down by impractical sequencing techniques, these drafts left out the most complex regions of our DNA, which make up around 8 percent of the total genome. This is because these sequences are highly repetitive and contain many duplicated regions – attempting to put them together in the right places is like trying to complete a jigsaw puzzle where all the pieces are the same shape and have no image on the front. Long gaps and underrepresentation of large, repeating sequences made it so that this genetic material has been excluded for the past 20 years. Scientists had to come up with more accurate methods of sequencing to illuminate the darkest corners of the genome.

Read more | >