
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...
07/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
07/05/2026
Cobalt Digital Wins Two Future Best of Show Awards at 2026 NAB Show
Manufacturer Recognized by TV Tech and TVBEurope for Innovation in signal processing
Cobal...
07/05/2026
Software and hardware platforms, AI power and user-friendliness on show...
07/05/2026
Intinor will demonstrate its latest technical enhancements for the Direkt series at BroadcastAsia 2026. With a continued focus on reliable contribution and remo...
07/05/2026
Bitmovin has announced that MUBI has chosen Bitmovin as its cloud VOD encoding partner, replacing MUBI's legacy on premises encoding setup to improve scalab...
07/05/2026
Meet Graduates from Berklees Class of 2026 Members of this years graduating class reflect on their proudest moments at Berklee and look ahead to whats next.
...
07/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
07/05/2026
At BroadcastAsia 2026, Interra Systems will demonstrate its latest innovations in automated quality control (QC), real-time monitoring, and captioning. The comp...
07/05/2026
At this year's Broadcast Asia, PlayBox Neo is set to unveil recent innovations across its PlayBox Neo Suite and integrated range of broadcast media solution...
07/05/2026
Strategic three-year partnership marks delivery phase of BFBS' next-generation media vision
Media organisation and military charity BFBS (British Forces Br...
07/05/2026
Amagi, the agentic industry cloud platform for unified broadcast, streaming, and monetization, today announced the availability of its In-Content Ads offering v...
07/05/2026
Lightware Visual Engineering has developed Rack Taurus for rack-based environments such as education and corporate training spaces. It enables clean and simple ...
07/05/2026
Jigsaw24, the UK's leading media equipment supplier and systems integrator, will showcase its expanded end-to-end workflow capabilities at MPTS 2026, signal...
07/05/2026
Ease Live, an Evertz company, today announced that it has been granted a US Patent for its proprietary graphical overlay technology, the foundation for interact...
07/05/2026
Test & measurement innovator Leader Electronics of Europe will present an extensive range of Leader, PHABRIX and LeaderPhabrix test and measurement solutions at...
07/05/2026
At Broadcast Asia 2026 (Stand 5H3 8), LiveU is redefining live production with its most powerful IP-video EcoSystem to date built to help broadcasters and con...
07/05/2026
January 8, 2024
Colorfront (colorfront.com), a leader in high-performance, on-s...
07/05/2026
February 9, 2024
Colorfront (colorfront.com), the multi-award-winning pioneer i...
07/05/2026
March 20, 2024
NAB 2024, Las Vegas - Colorfront (colorfront.com), the multi-awa...
07/05/2026
April 1, 2025
CINEMACON, APRIL 1, 2025 - Colorfront (colorfront.com), the multi-award-winning developer of high-performance dailies/transcoding/streaming syste...
07/05/2026
June 15, 2025
Colorfront (colorfront.com), an Academy and Emmy Award-winning de...
07/05/2026
June 15, 2025
Colorfront participated in the ICTA Barcelona Cinema Technology Summit on Sunday, June 15, 2025. Held at The Phenomena Experience, the event feat...
07/05/2026
July 1, 2025
Colorfront (colorfront.com), the multi-award-winning developer of high-performance dailies/transcoding/streaming systems for motion pictures, OTT,...
07/05/2026
July 1, 2025
Passion and dedication will take you places. Come with us on a short trip to the heart of India, where Annapurna Studios is living-up to the inspi...
07/05/2026
July 3, 2025
Colorfront (colorfront.com), the multi-award-winning developer of high-performance dailies/transcoding/streaming systems for motion pictures, OTT,...
07/05/2026
September 1, 2025
IBC 2025, Amsterdam - Colorfront (colorfront.com) - the Acade...
07/05/2026
April 17, 2026
LOS ANGELES - April 17, 2026 - Colorfront today announced Colorf...
07/05/2026
April 23, 2026
NAB 2026, Las Vegas - the Academy and Emmy Award-winning develop...
07/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
07/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
07/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
07/05/2026
Recreating the 1974 Doctor Who Time Tunnel in After Effects
Graham Quince May 6, 2026
0 Comments
The Time Tunnel from Doctor Who titles is one of th...
07/05/2026
Well known Irish faces pushed to the edge in new series of
Uncharted with Ray G...
07/05/2026
RT will premiere A Traveller Family, a compelling new documentary exploring the...
07/05/2026
Less typing, more tanking.
Faster logins mean more time in the gaming action - and this week provides GeForce NOW members with a smoother path straight into th...
06/05/2026
Gravity Media Chief RF Communications Engineer Glenn Willems uses Wisycom RF over Fiber and wireless solutions across major cycling events and international mar...
06/05/2026
A Sennheiser Spectera module is now available in Bitfocus Companion and Buttons, enabling direct integration of Spectera with the two software platforms. The mo...
06/05/2026
Ted Turner, the visionary media entrepreneur whose appetite for disruption helpe...
06/05/2026
Peacock is going all-in on the beautiful game - streaming all 104 FIFA World Cup...
06/05/2026
New pricing tiers for vocal/dialogue restoration tool
NoiseWorks Audio's AI-powered vocal and dialogue processing plug-in is now available in three diff...
06/05/2026
Popular mixing & routing software overhauled
Following a recent public beta test, RME have launched the final release version of the powerful mixing and rou...
06/05/2026
New SOS Video Feature
Focusrites ISA C8X is a milestone product that brings together the companys analogue heritage and their expertise in digital audio. Yo...
06/05/2026
Polands Miecznik-class frigates are part of the largest contract in Polish shipbuilding history. (Image Credit: PGZ Stocznia Wojenna)...
06/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
06/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
06/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...