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

09/11/2025

Dalet Unveils Agentic AI Media Workflows at IBC2025

Dalet today announced a transformative leap forward for media operations: Agentic Artificial Intelligence (AI) that unifies the Dalet ecosystem under one natura...

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 ...

18/09/2025

NWSL Brings on Victory+ as Rightsholder, Expands Deals With CBS and ESPN for 2026-27 Seasons

NWSL Brings on Victory as Rightsholder, Expands Deals With CBS and ESPN for 202...

18/09/2025

CBS Sports Travels to Far Reaches of Europe To Tell Clubs' Stories During 2025-26 Champions League Season

CBS Sports Travels to Far Reaches of Europe To Tell Clubs' Stories During 20...

18/09/2025

The Great Integration: How Sports Media Leaders Are Making MAM, Storage, and Cloud Systems Work Together

The Great Integration: How Sports Media Leaders Are Making MAM, Storage, and Clo...

18/09/2025

Amazon Prime Video Launches Prime Vision for Champions League Coverage in UK

Amazon launches Prime Vision for Champions League coverage By George Bevir Tuesday, September 16, 2025 - 18:28 Print This Story Amazon is rolling out its ...

18/09/2025

SVG Sit-Down: Canon USA's Rich Eilers, Yuji Tanaka Talk Novel' Feature, EOS C50 Camera

SVG Sit-Down: Canon USA's Rich Eilers, Yuji Tanaka Talk Novel' Feature,...

18/09/2025

NBC Sports Will Deploy a Pair of Dedicated Analysts On the Bench' for Peacock NBA Monday Games

NBC Sports Will Deploy a Pair of Dedicated Analysts On the Bench' for Peaco...

18/09/2025

WATCH: Be a Fly on the Wall for a Conversation Between Robert Redford and Michelle Satter

Editor's Note: The loss of our founder and friend Robert Redford, leaves us...

18/09/2025

From the Archives: Sundance Institute Founder Robert Redford on Why He's Always Believed in the Power of Documentary Filmmaking

Editor's Note: The loss of our founder and friend Robert Redford, leaves us...

18/09/2025

From the Archives: Revisit Robert Redford's Words of Wisdom

Robert Redford talks with Lab fellows at the 1981 Directors Lab | 1981 Unknown for Sundance Institute Editor's Note: The loss of our founder and friend ...

18/09/2025

Ed Sheeran's Play' Comes to Life With Spotify's Special Fan Event in London

Forget just hearing a new album; last night, London lived one. Together with Spo...

18/09/2025

Sony Music Group and Spotify Announce Expanded Multiyear Global Partnership

Spotify and Sony Music Group today announced an extension and expansion of their long-standing, successful global partnership. As part of their ongoing collabor...

18/09/2025

SBS Audio podcast helps new Australians keep their Head Above Water

SBS Audio podcast helps new Australians keep their Head Above Water 17 September, 2025 Media releases As Australia heads toward summer, comedians and good ...

18/09/2025

Football fans to watch the inaugural Australian Championship on SBS

Football fans to watch the inaugural Australian Championship on SBS 18 September, 2025 Media releases Images here SBS and Football Australia are delighted...

18/09/2025

L3Harris Scales Up Rocket Motor Testing at Camden Site

L3Harris's advanced large solid rocket motor eSR-73 is hot fire tested at the company's Camden, Arkansas site....

18/09/2025

The Gauge: Poland | August 2025

August, the last month of the summer vacation, brought stability to the amount of time spent in front of the TV screen. The data shows that Polish viewers watch...

18/09/2025

FCC Commissioner Gomez Blasts ABC for Suspending Jimmy Kimmel

WASHINGTON The controversy over ABC's decision to suspend Jimmy Kimmel, continues to heat up, with FCC Commissioner Anna M. Gomez blasting ABCs decision to ...

18/09/2025

FOR-A America Appoints Jo Aun to Lead US Product Developm...

FOR-A America named Jo Aun as Senior Manager of Product Management and Engineering, reporting directly to Satoshi Kanemura, President and COO. In this new posit...

18/09/2025

MASV Highlights Partner Integrations Fueling Modern Media...

MASV (massive.io), the fastest and most reliable large file transfer platform for media professionals and an IDC Innovator 2025 for Media & Entertainment*, toda...

18/09/2025

Dish TV India partners with ThinkAnalytics to power AI-dr...

ThinkAnalytics, the global leader in video content discovery and persaonalization, today announced that Dish TV India, the leading content distribution company,...

18/09/2025

DirecTV Adds Three Sports Channels to Its FAST Streaming Offering

DirecTV continues to expand its women's sports offerings by adding Sports Fanatics' and Whoopi Goldberg's Free Ad-Supported Television (FAST) All Wo...

18/09/2025

Fall Football Kicks Off With Native HDR Production, NextGen TV Telecast

WASHINGTON NextGen TV viewers are beginning to see what high dynamic range (HDR) brings to their football enjoyment with the launch of the sport's fall seas...

18/09/2025

FCC Extends Deadline for EEO Audit Replies

WASHINGTON After issuing audit letters seeking Equal Employment Opportunity data from a randomly selected group of TV and radio stations in August, the Federal ...

18/09/2025

Warner Bros. Discovery Signs New Deal with Nielsen

NEW YORK Warner Bros. Discovery and Nielsen have signed a new, long-term, multi-year deal that covers measurement for all Warner Bros. Discovery platforms acros...

18/09/2025

CIMM Launches Startup Program and Innovation Showcase

NEW YORK As part of its ongoing efforts to develop better measurement solutions, the Coalition for Innovative Media Measurement (CIMM) announced the launch of t...

18/09/2025

UPDATED: ABC Takes 'Jimmy Kimmel Live! Off the Air Indefinitely

IRVING, Texas Following threats from the Federal Communications Commission and the announcement that the nations largest station group, Nexstar Media Group, wou...

18/09/2025

VEON Inaugurates JazzCash Experience Lounge in Islamabad

18 Sep 2025 VEON Inaugurates JazzCash Experience Lounge in Islamabad Dubai and Islamabad, September 18, 2025 - VEON Ltd. (Nasdaq: VEON), a global digital opera...

18/09/2025

Natasha Lyonne and Matt Berry to star in new Sky Original action-adventure comedy Force & Majeure

Created by Tom Scharpling, Matt Berry and Natasha Lyonne, the new six-part serie...

18/09/2025

Niamh Algar and Tom Hollander star in Sky Original The Iris Affair full trailer released

The eight-part sun-drenched thriller from Luther creator Neil Cross launches on ...

18/09/2025

Rohde & Schwarz announces new frequency models up to 54 GHz for R&S ZNB3000 vector network analyzer

Rohde & Schwarz announces new frequency models up to 54 GHz for R&S ZNB3000 vect...

18/09/2025

RT Prime Time investigation uncovers location data of thousands of smartphones in Ireland for sale

Individual phones could be tracked back to specific residential addresses Sm...

18/09/2025

GeForce NOW Unleashes Dying Light: The Beast' in the Cloud

GeForce NOW is packing a monstrous punch this week. Dying Light: The Beast, the latest adrenaline fueled chapter in Techland's parkour meets survival horror...

18/09/2025

Dolby Atmos arrives in Maruti Suzuki Victoris, expanding premium in-car entertainment in India

September 18 2025, 04:20 (PDT) Dolby Atmos arrives in Maruti Suzuki Victoris, e...

17/09/2025

Tech Focus: Audio Training, Part 2 - Manufacturers Offer Extensive Online Learning

Tech Focus: Audio Training, Part 2 - Manufacturers Offer Extensive Online Learni...

17/09/2025

Tech Focus: Audio Training, Part 1 - A1 Shortage Remains a Major-League Challenge for Sports Broadcasting

Tech Focus: Audio Training, Part 1 - A1 Shortage Remains a Major-League Challeng...

17/09/2025

Dua Lipa's Service95 Book Club' Goes Live at the New York Public Library

It was the ultimate convergence of pop culture and literary prestige: Last night, Dua Lipa brought her Service95 Book Club podcast to the stage for a special li...

17/09/2025

The Gauge: Mexico August 2025

During August, streaming's share of TV viewing in Mexico showed an increase of 0.4% compared to the previous month, accounting for 25% of TV viewing. Discl...

17/09/2025

Jo Aun Joins FOR-A America as Senior Manager, Product Engineering

CYPRESS, Calif. FOR-A America has named Jo Aun as senior manager of product engineering, a new role responsible for guiding the planning, development and rollou...

17/09/2025

PlayBox Neo and CIS Group Power CazeTV with a seamless Pl...

PlayBox Neo, in partnership with CIS Group, a leading provider of media and broadcast technology solutions, has successfully deployed PlayBox Neo's Dual Cha...

17/09/2025

Energy Regulatory Agency Underscores Commitment with Ene...

In a relationship that mirrors societal advances in sustainability, Brightline Lighting and the Federal Energy Regulatory Commission (FERC) Headquarters have en...

17/09/2025

Clear-Com Powers Star-Studded Communications at Houston A...

Clear-Com is proud to support the world-class productions of Alley Theatre, one of the oldest and largest nonprofit resident theatres in the United States. With...

17/09/2025

Arch Platform Technologies Announces Strategic Collaborat...

Arch Platform Technologies (www.archpt.io), a pioneer in automated, scalable cloud infrastructure for high-performance workflows, today announced a Strategic Co...

17/09/2025

With over 39bn EUR in assets under management and record-...

Over 300 selected decision-makers from start-ups, corporates, and VC funds worldwide will gather for the third edition of the event, united by a single goal: to...

17/09/2025

Telestream Celebrates Award Win at IBC2025

Telestream, a global leader in media workflow technologies, is excited to announce that its flagship Vantage platform and its next-generation AI capabilities re...

17/09/2025

Mediagenix Celebrates Triple Best of Show Wins at IBC2025...

Mediagenix, a global leader in smart content solutions that profitably connect the right content to the right audience, proudly announces its three Best of Show...

17/09/2025

PlayBox Neo Appoints Transtel Universal as Top Reseller P...

In a move to further establish a firm foothold across South East Asia, PlayBox Neo, the well-respected name in broadcast playout and channel branding, has appoi...

17/09/2025

Wisycom Unveils Two New Solutions at IBC 2025

Wisycom, a global leader in advanced wireless audio solutions, announced two major wireless solutions at IBC 2025 (Stand 8.D30). This includes the Portable RF-o...

17/09/2025

Six Berklee Alumni Win Emmy Awards

Six Berklee Alumni Win Emmy Awards The recipients were recognized for their contributions to acclaimed programs Severance, The Studio, The Penguin, SNL50: The...

17/09/2025

Applications Open for Berklee in Santo Domingo

Applications Open for Berklee in Santo Domingo The weeklong contemporary music program will run January 5-10, 2026. By Colette Greenstein September 17, 2025 ...