Sony Pixel Power calrec Sony

May 20, 2024

21/05/2024

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
LINK: https://www.scripps.edu/news-and-events/press-room/2024/20240520-jin-b...
See more stories from scripps

Most recent headlines

06/10/2025

France Tlvisions Wins Prestigious 2025 EBU Technology & Innovation Award in Groundbreaking Collaboration with Dalet

France T l visions, France's leading broadcaster, has received the 2025 EBU ...

04/09/2025

Monumental Sports & Entertainment and Dalet Win Prestigious 2025 NAB Show Project of the Year Award

Monumental Sports & Entertainment (MSE), in collaboration with Dalet, has been a...

07/08/2025

Tata Motors & Dolby Bring Dolby Atmos to Harrier.ev, Redefining In-Car Entertainment Experience

July 8 2025, 22:30 (PDT) Tata Motors & Dolby Bring Dolby Atmos to Harrier.ev, R...

18/07/2025

Realm of Satan Disturbs the Comfortable at 2024 Sundance Film Festival

Blanche Barton, Peter Gilmore, Scott Cummings, Sundance Institute Director of Programming Kim Yutani, and Peggy Nadramia throwing horns. (Stephen Lovekin/Shutte...

18/07/2025

Give Me the Backstory: Get to Know Heidi Ewing and Rachel Grady, the Directors of FOLKTALES

By Jessica Herndon One of the most exciting things about the Sundance Film Fest...

18/07/2025

NESN Unveils Enhanced NESN 360 App for iOS, Android Devices

BOSTON Sports network NESN today relaunched the NESN 360 app with a redesigned user experience and upgrades....

18/07/2025

Berklee Singers Wow the Competition on Netflixs Building the Band

Berklee Singers Wow the Competition on Netflixs Building the Band Netflixs new music competition show features two Berklee artists looking to make their pop b...

18/07/2025

Trump Expected to Sign Bill Defunding CPB After House Approves $1B Cuts

As the House of Representatives voted early Friday morning to eliminate federal funding for public broadcasting, advocates warned that the elimination of $1 bil...

18/07/2025

Imagine Communications Sharpens Focus on Sports, Live Events Market

DENVER Imagine Communications has announced that it is deepening its commitment to the North American sports and live events market with investments in its prod...

18/07/2025

Netflix Beats Revenue, Profit Expectations

LOS GATOS, Calif. Netflix once again reported strong financial growth, with revenue increasing 16% year-over-year to $11.079 billion in Q2 2025 as net income s...

18/07/2025

Live from the 153rd Open Championship: SMT Enhances Video Board Experience; Enables Practice Scheduling for Players

Live from the 153rd Open Championship: SMT Enhances Video Board Experience; Enab...

18/07/2025

ShotTracker's Davyeon Ross on Revolutionizing Basketball On the Court and Beyond Through Tracking Tech

ShotTracker's Davyeon Ross on Revolutionizing Basketball On the Court and ...

18/07/2025

Home Pitch: How the Danish League Brought Its Live Match Production In-House

Home Pitch: How the Danish League Brought Its Live Match Production In-House Matchday Production produced 800+ matches across Denmark in its first year By Geor...

18/07/2025

Live From the 153rd Open Championship: EMG Debuts Spidercam for Golf, Expands Support for NBC Sports

Live From the 153rd Open Championship: EMG Debuts Spidercam for Golf, Expands Su...

18/07/2025

Usyk vs Dubois II: Bringing the Fight to Life with State of the Art Cameras and Graphics from DAZN and Gravity Media

Usyk vs Dubois II: Bringing the fight to life with state of the art cameras and ...

18/07/2025

Usyk vs Dubois II: DAZN's Head of Boxing Chris Glanville Talks Helicopters, a Ringwalk Spectacular and Directing the Action

Usyk vs Dubois II: DAZN's head of boxing Chris Glanville talks helicopters, ...

18/07/2025

Live From the 153rd Open Championship: NBC Expands Unilateral Effort; Shared Studio Gives Live From,' NBC Sports a Great View

Live From the 153rd Open Championship: NBC Expands Unilateral Effort; Shared Stu...

18/07/2025

Warner Bros. Discovery's Anne Graham on Training New Professionals to Ensure the Future of the Business

Warner Bros. Discovery's Anne Graham on Training New Professionals to Ensure...

18/07/2025

Live From the 153rd Open Championship: How R&A Spidercam Became a Reality for Golf Coverage

Live From the 153rd Open Championship: How R&A Spidercam Became a Reality for Go...

18/07/2025

ESPN Bulks Up Onsite Studios, Cameras, Player Mics for WNBA All-Star Weekend

ESPN Bulks Up Onsite Studios, Cameras, Player Mics for WNBA All-Star Weekend Besides the game, four studio shows will be produced onsite By Jason Dachman, Edit...

18/07/2025

The Sky Arts Awards Are Back, Live From The Roundhouse This September

Friday 18 July 2025 Credit: Marc Sethi The Sky Arts Awards will return on 16 September, once again taking place at the iconic Roundhouse in London. Produced b...

18/07/2025

2025-07-18

This month, players can dive into special crossover events featuring SpongeBob SquarePants in Snake.io+ and Crossy Road Castle, available exclusively on Apple A...

18/07/2025

Hurling Fans Flock Together for a Night of Craic agus Ceol on RT's Up For The Match this Saturday night

Up for the Match brings the fun, the passion-and a bit of Riverdance- tomorrow n...

17/07/2025

Realm of SatanDisturbs the Comfortable at 2024 Sundance Film Festival

Blanche Barton, Peter Gilmore, Scott Cummings, Sundance Institute Director of Programming Kim Yutani, and Peggy Nadramia throwing horns. (Stephen Lovekin/Shutte...

17/07/2025

Audiobooks+ Brings More Choice and Flexibility to Spotify Premium Subscribers

Spotify's goal with audiobooks is to help grow the publishing industry and create the best possible experience for booklovers, which is why we're launch...

17/07/2025

L3Harris to Expand Solid Rocket Motor Production in Arkansas

An advanced large solid rocket motor hot fire test conducted at L3Harris' Camden, Arkansas, site....

17/07/2025

L3Harris Has the Future of PNT Ready Now

L3Harris payloads and components have been on board every U.S. GPS satellite-more than 70 missions since the 1970s. Our technology is at the core of GPS availab...

17/07/2025

L3Harris Introduces Launched Effects Vehicles to Increase US Multi-Domain Superiority

L3Harris' pack of launched effects is comprised of multi-role vehicles that ...

17/07/2025

Nielsen taps Ryan Moore as Chief Business Officer of Gracenote

NEW YORK - July 17, 2025 - Gracenote, the content data business unit of Nielsen, has announced the appointment of Ryan Moore to the new role of Chief Business O...

17/07/2025

David Cohen Joins Miri Technologies as VP, Sales and Business Development

READING, Pa. Network technology startup Miri Technologies has added David Cohen as vice president, business development. He'll be tasked with expanding the ...

17/07/2025

Berklee Wins CASE Award for Standout Digital Campaign

Berklee Wins CASE Award for Standout Digital Campaign The Alumni Affairs team's Variations Signature Series earned recognition for offering an authentic p...

17/07/2025

Senate Votes to Strip Federal Funds for Public Broadcasting

Early Thursday morning, the U.S. Senate voted to cut federal funding for PBS and NPR in a bill that also included cuts for foreign aid. In a 51-48 vote, the act...

17/07/2025

British Innovation Leads the Way at IBC2025

GREAT Britain and Northern Ireland Pavilions across IBC2025 (12 15 September, RAI Amsterdam) feature a remarkable 34 companies, each providing unique, innovativ...

17/07/2025

SMPTE Forms Study Group on Content Provenance and Authenticity In Media

WHITE PLAINS, N.Y. The Society of Motion Picture and Television Engineers today introduced its Content Provenance and Authenticity (CPA) in Media Study Group (S...

17/07/2025

NBCU Reports Highest Sales Volume in History' for 2025-26 Upfronts

NEW YORK Despite widespread concerns about a soft advertising market, NBCUniversal said it closed its 2025-26 upfront negotiation cycle with a record ad sales v...

17/07/2025

Study: TV Ads Are Top Influencer of Older Adults Buying Retirement Homes

NEW YORK Television advertising remains an effective means to market and influence younger baby boomer and Generation X consumers approaching retirement age, ac...

17/07/2025

Service Electric Cable TV Deploys OpenVault PMN

ALLENTOWN, Pa. & JERSEY CITY, N.J. Service Electric Cable TV and OpenVault have announced that the operator is deploying the OpenVault Proactive Network Manage...

17/07/2025

FCC Chair Outlines Busy Summer Agenda That Includes Major EAS Vote

WASHINGTON Following up on his first major policy speech just two ago, Federal Communications Commission Chair Brendan Carr is promising to buck the usual summ...

17/07/2025

SES Receives All Required Regulatory Approvals to Complete Intelsat Acquisition

Luxembourg, 14 July 2025 - SES received the final regulatory approvals for the SES-Intelsat transaction, including the US Federal Communications Commission. O...

17/07/2025

Berklee Alumni Nominated for 2025 Emmy Awards

Berklee Alumni Nominated for 2025 Emmy Awards Twenty-seven Berklee alumni received nominations across categories in sound mixing, sound editing, and compositi...

17/07/2025

What We Watched the First Half of 2025

Back to All News What We Watched the First Half of 2025 Entertainment 17 July 2025 Global Link copied to clipboard Today, we're sharing our latest Eng...

17/07/2025

Vote for Ivory 3 American Concert D in the MIDI Innovation Awards!

Cast your vote in 2 categories for Ivory 3 American Concert DIvory 3 American Concert D is in the 2025 MIDI Innovation Awards and we are honored to be nominated...

17/07/2025

SVG Sit-Down: OpenDrives' Sean Lee, Michael Wilsker, and Jason Matousek on Evolving Data Management

SVG Sit-Down: OpenDrives' Sean Lee, Michael Wilsker, and Jason Matousek on E...

17/07/2025

Oracle's Geoff Tognetti on Staying Ahead of the AI Curve Through Further Adoption

Oracle's Geoff Tognetti on Staying Ahead of the AI Curve Through Further Ado...

17/07/2025

NBA's Summer League Is a Hot Bed of AI, Immersive Innovation Testing

NBA's Summer League Is a Hot Bed of AI, Immersive Innovation Testing Audio mixing, intelligent camera framing are among AI-driven efforts By Ken Kerschbaum...

17/07/2025

SVG's TranSPORT Conference Returns to NYC on Oct. 21; Register Today!

SVG's TranSPORT Conference Returns to NYC on Oct. 21; Register Today! By SVG Staff Thursday, July 17, 2025 - 8:29 am Print This Story | Subscribe St...

17/07/2025

Gravity Media Chosen as Group Name for Merged OB Business

Gravity Media chosen as group name for merged OB business By George Bevir Wednesday, July 16, 2025 - 11:30 Print This Story Gravity Media executive chairm...

17/07/2025

SES Closes Deal to Acquire Intelsat, Creating New Giant in Satellite Connectivity

SES Closes Deal to Acquire Intelsat, Creating New Giant in Satellite Connectivit...

17/07/2025

How MLB Pulled Off That Unforgettable Hank Aaron Tribute at the All-Star Game

How MLB Pulled Off That Unforgettable Hank Aaron Tribute at the All-Star Game Vintage content, state-of-the-art projection/processing combine in marvelous mile...

17/07/2025

Riedel Communications Powers Handa Opera on Sydney Harbour with Integrated Network and Comms Solutions

Wuppertal July 17, 2025 Riedel Communications Powers Handa Opera on Sydney Har...