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
Journalists reporting on Sudan are working in one of the most complex and fast-m...
07/05/2026
Multi-year partnership positions Victory+ as a free home for Dallas Cowboys orig...
07/05/2026
From sideline reporting to directing and producing, the talented sophomore is building a well-rounded foundation for a career in live sports production
In the ...
07/05/2026
Cobalt Digital has received two Future Best of Show awards at NAB Show 2026. The COBALT blueCORE platform was recognized by TV Tech, and the COBALT PACIFIC ULL-...
07/05/2026
ESPN analyst Mina Kimes will host the televised semifinals and finals of the 202...
07/05/2026
Bitmovin has announced that MUBI, the global film streaming platform, has selected Bitmovin as its cloud VOD encoding partner. Bitmovin's encoding infrastru...
07/05/2026
NBCUniversal Telemundo Enterprises and the U.S. Soccer Federation have announced...
07/05/2026
Angel City Football Club (ACFC) and Victory have announced a regional broadcast partnership bringing live match coverage to fans across the greater Los Angeles...
07/05/2026
Spiideo has announced the launch of AI Highlights inside Spiideo Play, its automated sports production platform. AI Highlights combines video, event data, audio...
07/05/2026
Leostream Corporation has announced a unified remote access ecosystem for high-p...
07/05/2026
The Atlanta Dream has partnered with Victory to stream all locally broadcast Dream games for free, expanding the team's digital distribution strategy and g...
07/05/2026
Riedel Communications has announced the appointment of Marc Engroff as Chief Fin...
07/05/2026
SES and ARD, Germany's largest public broadcasting network, have announced a long-term extension of their satellite distribution partnership through 2039. U...
07/05/2026
UpLight Technologies delivers a flexible video and lighting system for a new televised sportLaunching the Pro Cheer League required more than creating a compell...
07/05/2026
Full Day Productions and GSE Worldwide have announced Spikes Under the Lights, a...
07/05/2026
Seit dem Start im Jahr 2023 hat DJ (Beta) das personalisierte H rerlebnis von 94...
07/05/2026
Da quando stata presentata nel 2023, DJ (beta) ha aiutato a definire un'esperienza d'ascolto pi personalizzata per 94 milioni di utenti Spotify Premi...
07/05/2026
Since launching in 2023, DJ (beta) has helped shape a more personalized listenin...
07/05/2026
Desde o lan amento em 2023, o DJ (beta) j ajudou a deixar a experi ncia de ouvi...
07/05/2026
From our earliest days, Spotify has been built on a simple principle: Great audio should be easy to reach. It's what's driven us to expand from music to...
07/05/2026
Asian and Pacific Islander artists continue to shape the global soundscape, pushing creative boundaries and connecting with fans worldwide. This Asian & Pacific...
07/05/2026
Company announce long-requested choir instrument
In the latest expansion of their Symphonic Elements series, UJAM have introduced an all-new vocal instrumen...
07/05/2026
Modular-inspired sound generation with digital control
Buchla have introduced Ziggy, a new compact synthesizer built around the company's complex oscill...
07/05/2026
Combines analogue voices with digital synthesis and sequencing
Polyend have announced Drums, a new hybrid analogue and digital drum machine that combines sy...
07/05/2026
Control surface now officially supports four DAWs
When Nektar launched the Panorama CS12 control surface, it worked exclusively with Apple's Logic Pro, ...
07/05/2026
In the first quarter 2026, SGL Carbon generated consolidated sales of 184.5 million, which was 49.8 million, or 21.3%, lower than in the prior year (Q1 2025: ...
07/05/2026
Rohde & Schwarz and Greenerwave achieve precise and fast ESA antenna characteriz...
07/05/2026
Two multi-role L3Harris products - the Red Wolf launched effects vehicle and SK...
07/05/2026
L3Harris will be developing key features of a secure and resilient digital infra...
07/05/2026
Alysa Liu and Shohei Ohtani Help Drive Viewership as 91 of the Top 100 Broadcast...
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...
New method to reveal what drives brain diseases Scripps Research scientists develop CRISPR screen technology to determine disease mechanism from tissues with accelerated speed. 
