New method to reveal what drives brain diseases Scripps Research scientists develop CRISPR screen technology to determine disease mechanism from tissues with accelerated speed.
May 20, 2024
LA JOLLA, CA The brain is often referred to as a black box one that's difficult to peer inside and determine what's happening at any given moment. This is part of the reason why it's difficult to understand the complex interplay of molecules, cells and genes that underly neurological disorders. But a new CRISPR screen method developed at Scripps Research has the potential to uncover new therapeutic targets and treatments for these conditions.
The method, outlined in a study published in Cell on May 20, 2024, provides a way to rapidly examine the brain cell types linked to key developmental genes at a scale never done before helping unravel the genetic and cellular drivers of different neurological diseases.
We know that certain genetic variants in our genome can make us vulnerable or resilient towards different diseases, but which specific cell types are behind a disease? Which brain regions are susceptible to the genome mutations in those cells? These are the kinds of questions were trying to answer, says senior author Xin Jin, PhD, an assistant professor in the Department of Neuroscience at Scripps Research. With this new technology, we want to build a more dynamic picture across brain region, across cell type, across the timing of disease development, and really start understanding how the disease happened and how to design interventions.
Thanks to over a decade's efforts in human genetics, scientists have had access to long lists of genetic changes that contribute to a range of human illnesses, but knowing how a gene causes a disease is very different than knowing how to treat the illness itself. Every risk gene may impact one or several different cell types. Comprehending how those cell types and even individual cells impact a gene and affect disease progression is key to understanding how to ultimately treat that disease.
This is why Jin, along with the study's first author, Xinhe Zheng, a PhD candidate and the Frank J. Dixon Graduate Fellow at Scripps Research, co-invented the new technique, named in vivo Perturb-seq. This method leverages CRISPR-Cas9 technology and a readout, single-cell transcriptomic analysis, to measure its impact on a cell: one cell at a time. Using CRISPR-Cas9, scientists can make precise changes to the genome during brain development, and then closely study how those changes affect individual cells using single-cell transcriptomic analysis for thousands of cells in parallel.
Our new system can measure individual cells' response after genetic perturbations, meaning that we can paint a picture of whether certain cell types are more susceptible than others and react differently when a particular mutation happens, Jin says.
Previously, the method for introducing the genetic perturbations into the brain tissue was very slow, often taking days or even weeks, which created suboptimal conditions for studying gene functions related to neurodevelopment. But Jin's new screening method allows for rapid expression of perturbation agents in living cells within 48 hours meaning scientists can quickly see how specific genes function in different types of cells in a very short amount of time.
The method also enables a level of scalability that was previously impossible the research team was able to profile more than 30,000 cells in just one experiment, 10-20 times accelerated from the traditional approaches. In many of the brain regions they examined, such as the cerebellum, they were able to collect tens of thousands of cells that previous labeling methods could not reach.
In a pilot study using this new technology, Jin and her team's interest was piqued when they saw a genetic perturbation elicit different effects when perturbed in different cell types. This is important because those impacted cell types are the sites of action for particular diseases or genetic variants. Despite their smaller population representations, some low-abundant cell types may have a stronger impact than others by the genetic perturbation, and when we systematically look at other cell types across multiple genes, we see patterns. That's why single-cell resolution being able to study every cell and how each one behaves can offer us a systematic view, Jin says.
With her new technology in hand, Jin plans to apply it to better understand neuropsychiatric conditions and how certain cell types correspond with various brain regions. Moving forward, Jin says she's excited to see this type of technology applied to additional cell types in other organs in the body to better understand a wide range of diseases in terms of tissue, development and aging.
This work and the researchers involved were supported by funding from the Dorris Scholar Award, the Frank J. Dixon Fellowship, the Mark Pearson Endowed Fellowship, the Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard, the Simons Foundation Autism Research Initiative (grant SFARI #736613), the National Institute of Health (grant R01HG012819), the Impetus grant, the One Mind Rising Star Award, the Klingenstein-Simons Fellowship, the Mathers Foundation, the Baxter Young Investigator Award, the Larry L. Hillblom Foundation, the Scripps Research Collaborative Innovation Fund, the Chan Zuckerberg Initiative, the Conrad Prebys Foundation, the Astera Institute, and James Fickle.
In addition to Jin, authors of the study, Massively parallel in vivo Perturb-seq reveals cell type-specific transcriptional networks in cortical development are Xinhe Zheng, Boli Wu, Yuejia Liu, Grace S. Clarke, Abdullah Ashiq, Joshua Park, Jiwen Li, Zhilin Wang, Tianbo Qi and Yunxiao Zhang of Scripps Resear
Most recent headlines
05/01/2027
Worlds first 802.15.4ab-UWB chip verified by Calterah and Rohde & Schwarz to be ...
04/08/2026
Dalet, a leading technology and service provider for media-rich organizations, t...
04/07/2026
April 7 2026, 19:00 (PDT) Detective Conan: Fallen Angel of the Highway Opens in...
01/06/2026
January 6 2026, 05:30 (PST) Dolby Sets the New Standard for Premium Entertainment at CES 2026
Throughout the week, Dolby brings to life the latest innovatio...
29/05/2026
With InfoComm 2026 just weeks away, NDI is giving attendees plenty of reasons to...
29/05/2026
Reaffirming a partnership that has defined Canadian sports broadcasting since 19...
29/05/2026
Mobile/tablet is No. 2 device for watching TV, suggesting that the sports-production industry needs to take another look at the format
Ring Digital's Sprin...
29/05/2026
Berliner Ensemble, one of Berlin's five major theater companies, has expande...
29/05/2026
Solid State Logic will showcase its new compact, fly-away TCA Tour audio product...
29/05/2026
Gerald (Jerry) Pierce, a pioneering technologist who helped shape the digital transformation of the motion picture industry, passed away last month on April 12 ...
29/05/2026
Paramount+ will be the English-language U.S. home for Barclays Women's Super...
29/05/2026
Further strengthening its virtualisation strategy to fully support broadcasters ...
29/05/2026
Swiss broadcaster Canal Alpha has deployed Harmonic's award-winning, software-based XOS Advanced Media Processor to modernize playout operations across cant...
29/05/2026
PTZOptics will showcase a new generation of intelligent video workflows at InfoComm 2026, June 17-19, Las Vegas. Visitors to booth N8227 will see how PTZOptics ...
29/05/2026
Arizona's Family has launched the Arizona's Family Sports (AZFS) streaming app, a new direct-to-consumer destination for live, local sports. The app is ...
29/05/2026
Starting in 2027, DAZN will be the exclusive home of The Canadian Football Leagu...
29/05/2026
Comcast Business has detailed the advanced network infrastructure it has deploye...
29/05/2026
In two-day event, leaders from academia and industry explored solutions to chall...
29/05/2026
The Basketball Tournament (TBT), now entering their 13th year of competition, ha...
29/05/2026
Roku has launched FOX One as a Premium Subscription on The Roku Channel in the U.S. Roku customers can now subscribe to FOX One using their Roku account for liv...
29/05/2026
In its sixth year, the broadcaster's coverage has become a global brand and ...
29/05/2026
Ratings Roundup is a rundown of recent ratings news and is derived from press re...
29/05/2026
The days are getting longer, the temperatures are rising, and playlists are filling up for the season. With summer around the corner, Spotify's global edito...
29/05/2026
New retro-inspired MPC announced
There are few devices that have gained the status held by Akai Pro's MPC range, and in recent years, the company have s...
29/05/2026
Save up to 30 on acclaimed titles
Following a successful launch at Superbooth 2026, Bjooks have revealed that they will be continuing the Kickstarter campa...
29/05/2026
Binaural monitoring application improved
Genelec have just released an update that brings some powerful new features to their HRTF-based binaural headphone ...
29/05/2026
6 June 2026 at SAE Institute, London, UK
IMSTA FESTA 2026 is almost upon us, with some of the biggest names in pro-audio set to descend upon SAE Institute i...
29/05/2026
Gerald (Jerry) Pierce, a pioneering technologist who helped shape the digital transformation of the motion picture industry, died April 12, 2026, at his home in...
29/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
29/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
29/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
29/05/2026
Comparing 5 AI Video Enhancers for Restoring Old Video Quality
Kate Luvis May 29, 2026
0 Comments
Digitizing VHS, MiniDV, and other legacy formats doe...
29/05/2026
Studio Hamburg Builds New Post Pipeline with DaVinci Resolve Studio
Brie Clayton May 29, 2026
0 Comments
Workflow replaces a patchwork of legacy tools...
29/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
29/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
29/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
29/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
29/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
29/05/2026
At the Intersection of Music and Dance, an Epic Collaboration Boston Conservatory musicians and dancers found creative parallels in their recent performance o...
29/05/2026
Something fundamental has shifted in how people consume media. Audiences aren't abandoning television or radio content; they're just expanding how, wher...
29/05/2026
Youtube exclusive special drops today
Watch now
UKTV today announces another e...
29/05/2026
Back to All News
The Official Trailer of Physical 100 Italy, on Netflix From Se...
29/05/2026
At just 20 years old, Sean Melia from Summerhill Co. Meath has been revealed as the winner of Super Garden 2026. Sean is the youngest ever contestant and winner...
29/05/2026
Experimental HIV vaccine achieves a long-sought goal In a first for the field, all non-human primates given a new series of vaccines generated antibodies capabl...
28/05/2026
Thomsons Climate Crisis Toolkit is already being put to work, helping journalist...
28/05/2026
FOX Sports' MLB coverage dominated the night at the 47th Annual Sports Emmy ...
28/05/2026
One of the most memorable postseasons in baseball history would have had no memo...
28/05/2026
NBC's Sunday Night Football is among the most-decorated and most-watched pro...
28/05/2026
The 2026 Sports Emmys marked a watershed moment for Prime Video Sports. After bu...
New method to reveal what drives brain diseases Scripps Research scientists develop CRISPR screen technology to determine disease mechanism from tissues with accelerated speed. 
