https://phys.org/news/2018-12-scientists-crispr-code-precise-human.html

Scientists crack the CRISPR code for precise human genome editing

December 13, 2018, The Francis Crick Institute
Scientists crack the CRISPR code for precise human genome editing
Illustration of the CRISPR/Cas9 genome editing system. Credit: Nigel Hawtin for the Francis Crick Institute

Scientists at the Francis Crick Institute have discovered a set of simple rules that determine the precision of CRISPR/Cas9 genome editing in human cells. These rules, published in Molecular Cell, could help to improve the efficiency and safety of genome editing in both the lab and the clinic.

Despite the wide use of the CRISPR system, rational application of the technology has been hindered by the assumption that the outcome of genome editing is unpredictable, resulting in random deletions or insertions of DNA regions at the target site.

Before CRISPR can be safely applied in the clinic, scientists need to make sure that they can reliably predict precisely how DNA will be modified.

“Until now, editing  with CRISPR has involved a lot of guesswork, frustration and trial and error,” says Crick group leader Paola Scaffidi, who led the study. “The effects of CRISPR were thought to be unpredictable and seemingly random, but by analysing hundreds of edits we were shocked to find that there are actually simple, predictable patterns behind it all. This will fundamentally change the way we use CRISPR, allowing us to study gene function with greater precision and significantly accelerating our science.”

By examining the effects of CRISPR genome editing at 1491 target sites across 450 genes in , the team have discovered that the outcomes can be predicted based on simple rules. These rules mainly depend on one genetic ‘letter’ occupying a particular position in the region recognized by the ‘guide RNA’ to direct the molecular scissors, Cas9 .

Guide RNAs are synthetic molecules made up of around 20 genetic letters (A,T,C,G), designed to bind to a specific section of DNA in the target gene. Each genetic letter has a complementary partner—A binds to T and C binds to G—which stick together a bit like Velcro. The guide RNA is like the ‘hook’ side of Velcro, designed to stick to the ‘loop’ side on the target gene.

Guided by the RNA molecule, the Cas-9 enzyme scans along the genome until it finds the region of interest. When the RNA guide matches the correct DNA sequence, it sticks like Velcro and Cas9 cuts through the DNA. The DNA is broken three letters from the end of the target sequence, and bits of genetic code are then inserted or deleted, seemingly haphazardly, when the cell attempts to repair the break.

In this study, the researchers found that the outcome of a particular gene edit depends on the fourth letter from the end of the RNA guide, adjacent to the cutting site. The team discovered that if this letter is an A or a T, there will be a very precise genetic insertion; a C will lead to a relatively precise deletion and a G will lead to many imprecise deletions. Thus, simply avoiding sites containing a G makes genome editing much more predictable.

“We were amazed to discover that the rules that determine the outcome of CRISPR human genome editing are so simple,” says Dr. Anob Chakrabarti, Wellcome Trust clinical Ph.D. fellow in the Crick’s Bioinformatics and Computational Biology lab and joint-first author of the study. “By bearing these rules in mind when designing our guide RNAs, we can maximise the chances of getting the desired outcome of a specific gene edit—which is particularly important in a clinical context.”

The team also discovered that how ‘open’ or ‘closed’ the target DNA is also affects the outcome of gene editing. Adding compounds that force DNA to open up—allowing Cas9 to scan the genome—led to more efficient editing, which could help when modifications need to be introduced in particularly closed genes.

“The good news is that regardless of the tissue of origin—which influences the degree of DNA ‘openness’ at specific genes—target regions containing an A or T at the key position show common editing,” says Paola. “This means that, if we carefully select the target DNA, we can be pretty confident that we’ll see the same effect in different tissues.”

Josep Monserrat, Crick Ph.D. student in the Cancer Epigenetics lab and joint-first author of the study, says: “We hadn’t previously appreciated the significance of DNA openness in determining the efficiency of CRISPR  editing. This could be another factor to consider when aiming to edit a gene in a specific way. We are excited to observe that distinct cell types share common editing at precise target regions, and hope translation of our findings will be beneficial across disciplines.”

 Explore further: Largest study of CRISPR-Cas9 mutations creates prediction tool for gene editing

More information: Molecular Cell (2018). DOI: 10.1016/j.molcel.2018.11.031

Read more at: https://phys.org/news/2018-12-scientists-crispr-code-precise-human.html#jCp

https://www.ctvnews.ca/health/heavy-screen-time-appears-to-impact-childrens-brains-study-1.4211371

Heavy screen time appears to impact childrens’ brains: study

Screen timeA new study advises limits on screen time for children and teenagers to help boost their well-being.(PeopleImages / IStock.com)

Published Monday, December 10, 2018 1:42AM EST 

Researchers have found “different patterns” in brain scans among children who record heavy smart device and video game use, according to initial data from a major ongoing U.S. study.

The first wave of information from the $300 million National Institute of Health (NIH) study is showing that those nine and 10-year-old kids spending more than seven hours a day using such devices show signs of premature thinning of the cortex, the brain’s outermost layer that processes sensory information.

“We don’t know if it’s being caused by the screen time. We don’t know yet if it’s a bad thing,” said Gaya Dowling, an NIH doctor working on the project, explaining the preliminary findings in an interview with the CBS news program 60 Minutes.

“What we can say is that this is what the brains look like of kids who spend a lot of time on screens. And it’s not just one pattern,” Dowling said.

The NIH data reported on CBS also showed that kids who spend more than two hours a day on screens score worse on language and reasoning tests.

The study — which involves scanning the brains of 4,500 children — eventually aims to show whether screen time is addictive, but researchers need several years to understand such long-term outcomes.

“In many ways, the concern that investigators like I have is, that we’re sort of in the midst of a natural kind of uncontrolled experiment on the next generation of children,” Dimitri Christakis, a lead author of the American Academy of Pediatrics’ most recent guidelines on screen time, told 60 Minutes.

Initial data from the study will begin to be released in early 2019.

The academy now recommends parents “avoid digital media use — except video chatting — in children younger than 18 to 24 months.”

https://www.sciencedaily.com/releases/2018/12/181204131047.htm

New building block in quantum computing demonstrated

Date:
December 4, 2018
Source:
DOE/Oak Ridge National Laboratory
Summary:
Researchers have demonstrated a new level of control over photons encoded with quantum information. The team’s experimental system allows them to manipulate the frequency of photons to bring about superposition, a state that enables quantum operations and computing.
The researchers’ innovative experimental setup involved operating on photons contained within a single fiber-optic cable. This provided stability and control for operations producing entangled photons, shown separated at top and intertwined at bottom after operations performed by the processor (middle), and further demonstrated the feasibility of standard telecommunications technology for linear optical quantum information processing.
Credit: Andy Sproles/Oak Ridge National Laboratory, U.S. Department of Energy

Researchers with the Department of Energy’s Oak Ridge National Laboratory have demonstrated a new level of control over photons encoded with quantum information. Their research was published in Optica.

Joseph Lukens, Brian Williams, Nicholas Peters, and Pavel Lougovski, research scientists with ORNL’s Quantum Information Science Group, performed distinct, independent operations simultaneously on two qubits encoded on photons of different frequencies, a key capability in linear optical quantum computing. Qubits are the smallest unit of quantum information.

Quantum scientists working with frequency-encoded qubits have been able to perform a single operation on two qubits in parallel, but that falls short for quantum computing.

“To realize universal quantum computing, you need to be able to do different operations on different qubits at the same time, and that’s what we’ve done here,” Lougovski said.

According to Lougovski, the team’s experimental system — two entangled photons contained in a single strand of fiber-optic cable — is the “smallest quantum computer you can imagine. This paper marks the first demonstration of our frequency-based approach to universal quantum computing.”

“A lot of researchers are talking about quantum information processing with photons, and even using frequency,” said Lukens. “But no one had thought about sending multiple photons through the same fiber-optic strand, in the same space, and operating on them differently.”

The team’s quantum frequency processor allowed them to manipulate the frequency of photons to bring about superposition, a state that enables quantum operations and computing.

Unlike data bits encoded for classical computing, superposed qubits encoded in a photon’s frequency have a value of 0 and 1, rather than 0 or 1. This capability allows quantum computers to concurrently perform operations on larger datasets than today’s supercomputers.

Using their processor, the researchers demonstrated 97 percent interference visibility — a measure of how alike two photons are — compared with the 70 percent visibility rate returned in similar research. Their result indicated that the photons’ quantum states were virtually identical.

The researchers also applied a statistical method associated with machine learning to prove that the operations were done with very high fidelity and in a completely controlled fashion.

“We were able to extract more information about the quantum state of our experimental system using Bayesian inference than if we had used more common statistical methods,” Williams said.

“This work represents the first time our team’s process has returned an actual quantum outcome.”

Williams pointed out that their experimental setup provides stability and control. “When the photons are taking different paths in the equipment, they experience different phase changes, and that leads to instability,” he said. “When they are traveling through the same device, in this case, the fiber-optic strand, you have better control.”

Stability and control enable quantum operations that preserve information, reduce information processing time, and improve energy efficiency. The researchers compared their ongoing projects, begun in 2016, to building blocks that will link together to make large-scale quantum computing possible.

“There are steps you have to take before you take the next, more complicated step,” Peters said. “Our previous projects focused on developing fundamental capabilities and enable us to now work in the fully quantum domain with fully quantum input states.”

Lukens said the team’s results show that “we can control qubits’ quantum states, change their correlations, and modify them using standard telecommunications technology in ways that are applicable to advancing quantum computing.”

Once the building blocks of quantum computers are all in place, he added, “we can start connecting quantum devices to build the quantum internet, which is the next, exciting step.”

Much the way that information is processed differently from supercomputer to supercomputer, reflecting different developers and workflow priorities, quantum devices will function using different frequencies. This will make it challenging to connect them so they can work together the way today’s computers interact on the internet.

This work is an extension of the team’s previous demonstrations of quantum information processing capabilities on standard telecommunications technology. Furthermore, they said, leveraging existing fiber-optic network infrastructure for quantum computing is practical: billions of dollars have been invested, and quantum information processing represents a novel use.

The researchers said this “full circle” aspect of their work is highly satisfying. “We started our research together wanting to explore the use of standard telecommunications technology for quantum information processing, and we have found out that we can go back to the classical domain and improve it,” Lukens said.

Lukens, Williams, Peters, and Lougovski collaborated with Purdue University graduate student Hsuan-Hao Lu and his advisor Andrew Weiner. The research is supported by ORNL’s Laboratory Directed Research and Development program.

Story Source:

Materials provided by DOE/Oak Ridge National LaboratoryNote: Content may be edited for style and length.


Journal Reference:

  1. Hsuan-Hao Lu, Joseph M. Lukens, Nicholas A. Peters, Brian P. Williams, Andrew M. Weiner, Pavel Lougovski. Quantum interference and correlation control of frequency-bin qubitsOptica, 2018; 5 (11): 1455 DOI: 10.1364/OPTICA.5.001455

Cite This Page:

DOE/Oak Ridge National Laboratory. “New building block in quantum computing demonstrated.” ScienceDaily. ScienceDaily, 4 December 2018. <www.sciencedaily.com/releases/2018/12/181204131047.htm>.