CRISPR-Cas guides the future of genetic engineering

 See all authors and affiliations

Science  31 Aug 2018:
Vol. 361, Issue 6405, pp. 866-869
DOI: 10.1126/science.aat5011


The diversity, modularity, and efficacy of CRISPR-Cas systems are driving a biotechnological revolution. RNA-guided Cas enzymes have been adopted as tools to manipulate the genomes of cultured cells, animals, and plants, accelerating the pace of fundamental research and enabling clinical and agricultural breakthroughs. We describe the basic mechanisms that set the CRISPR-Cas toolkit apart from other programmable gene-editing technologies, highlighting the diverse and naturally evolved systems now functionalized as biotechnologies. We discuss the rapidly evolving landscape of CRISPR-Cas applications, from gene editing to transcriptional regulation, imaging, and diagnostics. Continuing functional dissection and an expanding landscape of applications position CRISPR-Cas tools at the cutting edge of nucleic acid manipulation that is rewriting biology.

View Full Text

Nest investigates Hello doorbell issue that delays notifications

Delayed notifications caused users to miss packages and people at the door

Weird time-jumbling quantum device defies “before” and “after”

In normal life, you open the car door before getting into the car. Operation A happens before operation B. That’s the causal order of things. But a new quantum switch weirdly enables two operations to happen simultaneously. From Science News:

The device, known as a quantum switch, works by putting particles of light through a series of two operations — labeled A and B — that alter the shape of the light. These photons can travel along two separate paths to A and B. Along one path, A happens before B, and on the other, B happens before A.

Which path the photon takes is determined by its polarization, the direction in which its electromagnetic waves wiggle — up and down or side to side. Photons that have horizontal polarization experience operation A first, and those with vertical polarization experience B first.

But, thanks to the counterintuitive quantum property of superposition, the photon can be both horizontally and vertically polarized at once. In that case, the light experiences both A before B, and B before A, Romero and colleagues report.

While this is deeply weird and amazing, it unfortunately doesn’t occur at the human scale but rather in the quantum realm where measurements are in the nanometers. Still, quantum switches do have clear applications in future communications and computation systems.

Indefinite Causal Order in a Quantum Switch” (Physical Review Letters)

Firefox will soon block ad-tracking software by default

Image: Mozilla

Mozilla is taking a bold stance against more insidious web advertising practices with an announcement today that its Firefox browser will soon block web trackers by default. The move, which will involve a series of updates over the course of the next few months, is among one of the most proactive approaches to protect consumer privacy that it’s ever employed.

“Anyone who isn’t an expert on the internet would be hard-pressed to explain how tracking on the internet actually works,” reads the announcement posted to Mozilla’s blog. “Some of the negative effects of unchecked tracking are easy to notice, namely eerily-specific targeted advertising and a loss of performance on the web. However, many of the harms of unchecked data collection are completely opaque to users and experts alike, only to be revealed piecemeal by major data breaches.”

Mozilla says that web trackers will be disabled by default in the future, and Firefox users will have a series of controls to choose which information to share with which websites. In addition to protecting consumer privacy, Mozilla describes the decision as a way to also improve performance, as many web trackers inflate page load times. The organization cites a Ghostery study from May of this year that found that more than 50 percent of all time spent loading webpages was dedicated to loading third-party trackers designed to follow users around the web, collect data, and hand that data over to advertisers.

Mozilla’s approach will be three-fold. It’s going to study the effects of blocking trackers that slow page times starting next month, and it will make that feature on by default in Firefox 63 if it proves successful in improving performance. It will also “strip cookies and block storage access from third-party tracking content,” a move it will also test in September with beta users before implementing in Firefox 65, which is due out sometime in the next few months. Both of those features are available today for users of Firefox Nightly, which is the browser’s public pre-release channel for new features.

The third approach Mozilla is taking is to block by default newer and harder-to-detect practices like fingerprinting, which detects the type of device a user is using without their knowledge or consent, and cryptomining scripts that make use of excess computing power on a device to secretly generate digital currency.

This isn’t the first time Mozilla has pushed back against the web advertising industry. The organization blocked pop-up ads in the very first public Firefox release in 2004. Over the years, Mozilla has implemented features designed to promote consumer privacy and cut down on practices it sees as harmful to the open web, most notably the wholesale blocking of ads and trackers in private browsing mode starting in 2015.

Earlier this year, Mozilla released a tool to stop Facebook from tracking your online behaviorin the wake of the Cambridge Analytica data privacy scandal. That same month, it also gave users control of annoying web pop-up notifications.

“Some sites will continue to want user data in exchange for content, but now they will have to ask for it, a positive change for people who up until now had no idea of the value exchange they were asked to make,” reads Mozilla’s most recent announcement. “Blocking pop-up ads in the original Firefox release was the right move in 2004, because it didn’t just make Firefox users happier, it gave the advertising platforms of the time a reason to care about their users’ experience. In 2018, we hope that our efforts to empower our users will have the same effect.”

After leaking the new ‘iPhone XS’ in what appears to been an early test of its livestream, 9to5Mac has captured what looks to be the next Apple Watch Series 4.

Apple watch series 4 9to5mac

What we see is an Apple Watch which appears thinner, plus with a larger edge-to-edge display, showing more details than ever before on its watch face with numerous complications, now totalling 8, according to the picture.

The new Apple Watch Series 4 looks to be able to fit existing watch bands, while below the Digital Crown (which now has a single red ring to indicate LTE?) there appears to be another microphone. This looks like the Apple Watch people have been waiting for.

UBC researchers seek participants for perfectionism study


The need to be perfect, or appear to be perfect may be seen as a positive trait by some, but it can take a toll on mental health and require psychological treatment.

University of British Columbia researchers are seeking participants to take part in a new study looking at the effectiveness of a treatment for perfectionism developed by UBC Psychology Professor Paul Hewitt.

In this Q&A, Hewitt explains what perfectionism is, why it can be problematic for mental health, and how those interested can take part in the study.

Paul Hewitt

Paul Hewitt

What is perfectionism?

Perfectionism involves attempts to be perfect (i.e., perfect the self which is seen as flawed, defective, or not good enough) or to appear to others as perfect. It is not the same as being conscientious, achievement striving or striving for excellence, which are viewed as healthy traits. Rather, perfectionism is about correcting a perceived sense of being not good enough by being or appearing to be perfect.

Moreover, there are various mechanisms of perfectionism including traits, self-presentational facets (i.e., presenting oneself as perfect), and self-related cognitive and self-dialogue elements, meaning the inner dialogue one has with oneself that reflects the relationship one has with the self. These are all related to various kinds of psychological distress, dysfunction and disorders.

What are the possible treatment options for perfectionism?  

Over the past 25 years, we have been developing both individual and group treatments for perfectionism. This treatment focuses on the underlying mechanisms of perfectionism, as well as symptoms and problems. It is based on psychodynamic psychotherapy (which focuses on how a patient’s prior life experiences, particularly important relationships, influence their character and how they relate to others) as well as interpersonal psychotherapy (a common, in-person type of psychological treatment that centers on resolving interpersonal problems.)

What are you hoping to learn through this study?  

The current research is the second treatment study we have carried out to demonstrate the effectiveness and efficacy of the treatment. We are hoping to determine whether the treatment developed by our team is effective in comparison to another form of psychological treatment.

Individuals who are struggling with perfectionism and are interested in potentially participating in treatment can contact us to take part. They will be invited for a screening interview over the phone followed by an initial clinical assessment at the UBC Vancouver campus with one of the PhD clinical psychology students. During the assessment, participants will be asked to share the difficulties they are facing with perfectionism and related issues, and to complete some questionnaires. If eligible, individuals will participate in a 12-week group psychotherapy program.

Those interested in taking part in the study can contact the Hewitt Lab at 604-822-0932 or online at

New online tool will equip Canadian teachers to better support students’ mental health


Four Canadian universities, including the University of British Columbia, launched a new online curriculum resource earlier this month called Teach Mental Health. The site aims to expand mental health literacy among those studying to be teachers, and among those they teach. The resource is available to anyone who wants to learn more about youth mental health.

Wendy Carr of UBC’s faculty of education worked with colleagues from Dalhousie University, Western University and St. Francis Xavier University on the project. She explains how the online tool could help reduce the toll taken by mental illness.

Wendy Carr

Wendy Carr

What is meant by “mental health literacy”?

Mental health literacy has four pillars. The first is how to obtain, and maintain, good mental health. The second is learning about mental illness and treatment. The third is about reducing stigma. And the fourth is learning how and where to seek help for yourself and others.

Why did you develop this curriculum?

One of the top concerns for educators is the mental health of their students. Teachers are seeing more and more mental illness, just as we are in society — one in four adults lives with a mental illness. The onset of mental illness usually happens before the age of 25, and the adolescent years are when early intervention can make a real difference. We looked at what was available through Canadian faculties of education, and there really was nothing about mental health literacy. There’s been material for practicing teachers, but nothing for pre-service teachers. It’s really important for those going into education as a career to have this foundational literacy, so we’re filling that gap.

How can people use the resource?

It’s all online, available to anyone, and it’s free. There are seven modules, rich with explanatory videos and examples of classroom situations. There are activities for guiding your own learning, doing group learning, or as part of a teacher education program course. There is a logical sequence with a beginning and end, but you can dive in anywhere you like.

What outcomes do you hope for? 

I really hope that it furthers a level of mental health literacy among teachers, the children they teach, and the systems in which they work. Now teachers, particularly of secondary-age and middle-years students, can learn about some of the things to look for, how to reduce stigma, how to use appropriate language, and how and where to reach out for help. These can go a long way toward reducing those negative statistics, because the earlier you can identify mental illness, the better the outcomes for people and their chances to reach their full potential.

CRISPR is too fat for many therapies, so scientists are putting the genome editor on a diet


The Cas9 enzyme, key to the CRISPR system, has a lot of fat that it can lose and still serve as a powerful tool.

COLD SPRING HARBOR, NEW YORK—The genome editor CRISPR has morphed over the past 6 years from an obscure bacterial immune mechanism into the rock star tool of biology, allowing researchers to alter DNA with greater precision and ease than ever before. But the most popular version of CRISPR is simply too big, which complicates reaching some targets—and limits the ability of this powerful technology to create new therapies. Now, researchers have devised a way to put CRISPR on a diet and still retain its core functions.

Standard CRISPR methods have appropriated a DNA-snipping protein called SpCas9 from the Streptococcus pyogenes bacterium. Another CRISPR component guides the enzyme to targeted places on the genome. SpCas9 binds the DNA and its molecular scissors clip the double-stranded helix. But this lab darling, which has 1368 amino acids, is too chunky for many biomedical applications. So a team led by David Savage of the University of California, Berkeley, has devised a huge library of slimmer Cas9s using a “directed evolution” scheme.

“This is an amazing story because it’s a reversal of the actual evolutionary process,” says Kira Makarova, a pioneering CRISPR researcher at the National Center for Biotechnology Information in Bethesda, Maryland, who was not involved in the new work.

Savage, a structural biologist who presented his group’s work last week at the annual Cold Spring Harbor Laboratory CRISPR meeting here, calls the protein engineering method Minimization by Iterative Size-Exclusion Recombination (MISER). The technique uses two enzymes to systematically snip the DNA of the SpCas9 gene, pulling out chunks encoding different parts of the protein. Savage and colleagues then test those genetic sequences to see whether their resultant proteins still retain Cas9’s ability to bind to DNA targets. They then combine the ones that succeed, to add to the unique truncated options. So far, they have made half a million variants. “Shockingly, it works really well,” Savage says. “I didn’t expect it to be so flexible that it could tolerate enormous deletions and those could be stacked together.”

The MISER mutants won’t necessarily be able do everything that the typical CRISPR-Cas9 system can. One handicap is that some of the mutant Cas9s can lock onto an exact spot in the genome but cannot cut the DNA. But researchers earlier found that these “dead” Cas9s are handy tools, too, as they can ferry other molecules to specific destinations; one particularly powerful CRISPR technology called base editing exploits this to shuttle an enzyme to a target site that can convert one DNA base into another. The smallest MISER Cas9 mutant created to date—which can’t cut—has only 880 amino acids, about two-thirds the size of the original SpCas9.

Harvard University chemist David Liu, whose lab invented the base editor system, says Savage’s work with MISER is an “an outstanding early application of this exciting new method—and moves the genome editing field closer to a long-standing goal.”

Many investigators using CRISPR to design biomedical treatments package the genes for Cas9 and its other component inside a harmless virus that can shuttle them to specific cells to repair genetic defects. But the viruses have a limit to how much genetic cargo they can carry, and that’s where the skinny Cas9 could help tremendously—especially if its scissors work. “We have to finish this story,” says Savage, whose team is now sifting through its creations to find out which ones get the biggest bang for the smallest size.

Posted in:


Google Home gaining more visual Assistant responses on Chromecast-connected TVs

Earlier this year, Google Home began visualizing responses to certain queries when connected to a television via Chromecast. Google Assistant is now expanding the number of visual responses that will be overlaid on a big screen, while making voice Casting more seamless.

Back in February, asking “Hey Google, show me the weather on my TV” started overlaying a forecast on the bottom half of your screen. It includes the current location, temperature, condition, highs/lows, chance or precipitation, and humidity, as well as a five-day outlook. Visuals to complement voice commands was first announced at I/O 2017.

Another visualization later that month displayed a list of YouTube videos for easier browsing and selection via voice. Overlays appear on both the Ambient Mode and whatever content you happen to be Casting. It will disappear after Home finishes responding or in a few seconds when displaying over wallpaper.

Google at IFA 2018 is announcing visual responses for more types of queries, including sports scores, stocks, and others that benefit from a visual aid due to the amount of information being conveyed. When Voice Match is enabled, Assistant can provide personalized answers for you, like Calendar appointments.

Additionally, you no longer have to preface your commands with what screen content should be Casted on. For example, if a Chromecast-connected TV is already set as the default, users can just say “Hey Google, play The Office,” instead of, “Hey Google, play The Office on Living Room TV.”