Мобильный 1 Add news
March 2010
April 2010
May 2010June 2010July 2010
August 2010
September 2010October 2010
November 2010
December 2010
January 2011
February 2011March 2011April 2011May 2011June 2011July 2011August 2011September 2011October 2011November 2011December 2011January 2012February 2012March 2012April 2012May 2012June 2012July 2012August 2012September 2012October 2012November 2012December 2012January 2013February 2013March 2013April 2013May 2013June 2013July 2013August 2013September 2013October 2013November 2013December 2013January 2014February 2014March 2014April 2014May 2014June 2014July 2014August 2014September 2014October 2014November 2014December 2014January 2015February 2015March 2015April 2015May 2015June 2015July 2015August 2015September 2015October 2015November 2015December 2015January 2016February 2016March 2016April 2016May 2016June 2016July 2016August 2016September 2016October 2016November 2016December 2016January 2017February 2017March 2017April 2017May 2017June 2017July 2017August 2017September 2017October 2017November 2017December 2017January 2018February 2018March 2018April 2018May 2018June 2018July 2018August 2018September 2018October 2018November 2018December 2018January 2019February 2019March 2019April 2019May 2019June 2019July 2019August 2019September 2019October 2019November 2019December 2019January 2020February 2020March 2020April 2020May 2020June 2020July 2020August 2020September 2020October 2020November 2020December 2020January 2021February 2021March 2021April 2021May 2021June 2021July 2021August 2021September 2021October 2021November 2021December 2021January 2022February 2022March 2022April 2022May 2022June 2022July 2022
12
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
News Every Day |

Scientists Used CRISPR to Trace Every Human Gene to Its Function

CRISPR genetics genotype to phenotype map

Genes are like Egyptian hieroglyphs. Thanks to advances in whole-genome sequencing, it’s increasingly easy to read each DNA letter. But the strings of A, T, C, and G bring up a second puzzle: what, if anything, do they mean?

It’s a problem that has haunted biologists since the completion of the Human Genome Project. By tapping into our genetic base code, the project assumed, we’d be able to master control of inherited diseases, edit them at will, and easily predict the consequences of any gene that laid the foundation for our bodies, functions, and lives.

The vision didn’t exactly work out. DNA sequences, while capturing extremely powerful genetic information, don’t necessarily translate to indicating how our bodies behave. Genes can turn on or off in different tissues depending on the cell’s need. Reading a DNA sequence for any gene is like parsing the base code of a cell’s internal program. There’s the raw genetic code—the genotype—which determines the phenotype, life’s software that controls how cells behave. Linking the two has taken decades of painstaking experiments, slowly building up an encyclopedia of knowledge that decodes the influence of a gene on biological functions.

A new study ramped up the effort. Led by Drs. Thomas Norman and Jonathan Weissman at Memorial Sloan Kettering Cancer Center in New York and the University of California, San Francisco, respectively, the team built a Rosetta Stone for translating genotypes to phenotypes, with the help of CRISPR.

They went big. Changing gene expression in over 2.5 million human cells, the tech, dubbed Perturb-seq, comprehensively mapped how each genetic perturbation alters the cell. The technology centers around a sort of CRISPR on steroids. Once introduced into cells, Perturb-seq rapidly changes thousands of genes—a brutal shakeup at the genomic scale to see how single cells respond.

In other words, Perturb-seq is a large-scale tool that can help scientists translate DNA code to function—a Rosetta Stone for uncovering our cells’ inner workings. Years in the making, the dataset is open for anyone to explore.

“I think this dataset is going to enable all sorts of analyses that we haven’t even thought up yet by people who come from other parts of biology, and suddenly they just have this available to draw on,” said Norman.

Lost in Translation

What’s the function of a gene? It’s easy to think that genes are your destiny but that’s far from the truth. Environmental factors, such as a massive bowl of spaghetti or a walk along the beach, can easily change gene expression, bodily functions, and potentially your body and mind.

If that’s the case, what’s the point of sequencing whole genomes if the outcome is always in flux? “A central goal of genetics is to define the relationships between genotype and phenotype,” the authors said. In other words, what does any gene actually do?

Scientists have long sought to build a bridge between genotype and phenotype. It’s a painstaking process. One method, for example, perturbs genes that may be related to a disorder one by one and observes the cells’ behavior. Dubbed “forward genetics,” the idea is gene-focused rather than focusing on the phenotype. An alternative approach, “reverse genetics,” dives deep into how a body or mind changes with a specific genetic edit.

Each method is an uphill struggle. With over 20,000 genes in our bodies and every cell behaving slightly differently (even with the same genetic changes), deciphering a gene’s function often takes years, if not decades.

Is there any way to speed the process up?

The CRISPR Rosetta Stone

Enter CRISPR. Long revered as a genetic editing multitool, the method has further blossomed into a biological translator. At its heart is a technology dubbed Perturb-seq, first published in 2016 to dissect the expression of genes. Perturb-seq makes it possible to follow the consequences of turning a gene on or off in a single cell. The method rapidly rose to fame in 2020 for its efficiency at altering multiple genes at once.

It’s a huge win for cell biology, said the team. While scientists have readily chipped away at the massive web connecting genes and proteins, nailing down the role of individual genes has been a struggle. “We often take all the cells where ‘gene X’ is knocked down and average them together to look at how they changed,” said Weissman. “But sometimes when you knock down a gene, different cells that are losing that same gene behave differently, and that behavior may be missed by the average.”

The idea behind Perturb-seq is pretty simple. Imagine a toddler breaking stuff and realizing what he’s done after seeing the consequences. Perturb-seq uses CRISPR-Cas9 to silence multiple genes at once, which may sometimes change a cell’s behavior. While powerful, the tool has been hard to scale, studying at most a few hundred genetic perturbations at once for pre-defined biological questions.

So why not expand the method to the whole genome?

“The advantage of Perturb-seq is it lets you get a big dataset in an unbiased way,” said Norman. “No one knows entirely what the limits are of what you can get out of that kind of dataset. Now, the question is, what do you actually do with it?”

A Cell’s Life

In the new study, the team first found the magic sauce for making genome-wide changes in human cells with CRISPR. A major point was to optimize a library of guide RNAs (sgRNAs), the “bloodhounds” that track down a gene. Next, they captured cells infected with CRISPR and analyzed their gene expression. Overall, the team focused on nearly 2,000 genes. Cross-referencing changed genes with each cell’s phenotype, they then clustered genes into networks that linked to a cellular outcome.

One enigmatic gene stood out: C7orf26. Nixing it with CRISPR changed how a cell builds a huge molecular complex, dubbed the Integrator, which helps make molecules that control gene activity. Before Perturb-seq, C7orf26 had never been associated with the complex before.

In another analysis, the team found a subset of genes that changes how “daughter cells” inherit the parent genome. For example, removing some genes altered the distribution of chromosomes as a cell divides. Adding or removing a chromosome can fundamentally change our biology, such as by leading to Down Syndrome.

To Norman, this aspect is the most interesting part of Perturb-seq. “It captures a phenotype that you can only get using a single-cell readout. You can’t go after it any other way.”

This database is just the start. The team is looking to use Perturb-seq on other human cell types, and all the data is available for collaboration. With the rise of Ultima Genomics, an ultra-low-cost genomic sequencing solution, single-cell CRISPR screens are likely to play an even bigger role in biotechnology, such as in analyzing the genomes of iPSCs (induced pluripotent stem cells).

To Weissman, it may even spark a shift in how we approach cellular mysteries. “Rather than defining ahead of time what biology you’re going to be looking at, you have this map of the genotype-phenotype relationships, and you can go in and screen the database without having to do any experiments,” he said.

Image Credit: Jen Cook/Chrysos Whitehead Institute









Read also

Cardiac glycoside-mediated turnover of Na, K-ATPases as a rational approach to reducing cell surface levels of the cellular prion protein

UPI transactions shrink marginally in June vis-a-vis May

GM vehicle sales tumble 15% over chip crunch, supply chain snags


Прямой эфир РБК. Главные новости России и мира сегодня (Прямой эфир ежедневно)

News, articles, comments, with a minute-by-minute update, now on Today24.pro

News Every Day

Christian Thun faces Curtis Harper on July 9 ProBoxTV card in Florida

Today24.pro — latest news 24/7. You can add your news instantly now — here


News Every Day

Canadian Wood Council mass timber fire test performed as expected



Sports today


Новости тенниса
Уимблдон

Уимблдон. Карлос Алькараз отдал сопернику шесть геймов в третьем раунде соревнований



Спорт в России и мире
Москва

Когда и как оформить Fan ID?


Загрузка...

All sports news today




Загрузка...

Sports in Russia today

Москва

PEUGEOT SPORT И MARELLI ОБЪЯВИЛИ О ТЕХНИЧЕСКОМ ПАРТНЕРСТВЕ: В ФОКУСЕ — СОЗДАНИЕ ГИБРИДНОЙ СИЛОВОЙ УСТАНОВКИ ДЛЯ ГИПЕРКАРА 9X8


Новости России

Game News

Тройка от питерских: как «Зенит» разгромил ЦСКА в контрольном матче


Russian.city


Москва

Собянин осмотрел ход работ по строительству новой школы в ТиНАО


Губернаторы России
Выставка

Выставка уникальных гобеленов открылась во Владивостоке


Трубная продукция от «Энергопласт»

Колумнист Newsweek написала о возможности начала войны между Россией и США в Сирии

Мумие для здорового питания

Последние соседи Шатунова. Кто похоронен рядом со звездой «Ласкового мая»?


С сайта Полины Гагариной исчезло упоминание о концерте в Якутске

Лоза назвал Шатунова иностранным артистом

Стали известны подробности похорон Шатунова в Германии

Певец R. Kelly приговорен к 30 годам тюрьмы по делу о сексуальном насилии


"Челси" заинтересован в Зинченко

Специальный показ фильма «Андрей Рублев» пройдет в «Коломенском» 8 июля

Ричардас Беранкис: В нашем первом матче с Надалем я очнулся, когда уже уступал 1/4. Поэтому главное - держать концентрацию

Лиам Броуди: Сменил тактику по ходу матча со Шварцманом, а то он слишком доминировал с бэкхенда



Московские врачи за сутки вылечили 226 человек от коронавируса

Собянин рассказал о стремительном развитии Новой Москвы

За 10 лет в ТиНАО построено и реконструировано 10 очистных сооружений

Что с сайтом 123ru.net (нас читают и публикуются у нас). Уже более 70 млн. просмотров в мире.


К 2030 году количество выбросов в окружающую среду сократится на 40%

Том Круз, Брюс Уиллис и самые крутые киногерои – в эти выходные на ТВ-3

В Уфе в рамках акции «Каникулы с Росгвардией» олимпийский чемпион Семен Елистратов провёл мастер-класс с детьми

Звёздные артисты поют для «солнечных» детей: Прохор Шаляпин, Эвелина Блёданс, Наташа Королёва, Михаил Гребенщиков в новом детском спектакле «Осторожно – улица!»


В Московской области запустят еще одно производство газировки

В аэропорту Домодедово прошла акция "День донора" (Московский аэропорт "Домодедово")

В Подмосковье сократились случаи бешенства

За 10 лет в ТиНАО и на прилегающих территориях построено и реконструировано 335 км дорог



Путин в России и мире







Персональные новости
Russian.city

Полина Гагарина

С сайта Полины Гагариной исчезло упоминание о концерте в Якутске



News Every Day

Athletics’ Adrian Martinez will get starting assignment in Seattle




Friends of Today24


Загрузка...
Музыкальные новости
"Воскресенье " Олег Митяев



Персональные новости
Близкий друг Путина миллиардер Пугачев. Вся правда о Путине, его семье и деньгах. В гостях у Гордона (2021)

Навальный об уволенном за пост священнике (2021)

Slava Marlow – суперуспех и депрессия в 21 год / вДудь (2021)

Обнаглевшие дети путинской элиты (2021)

Дайте собакам мяса (новый звук) -Владимир Высоцкий

Группа "Рождество" - песня "Так хочется жить!" (Видео с концерта в Киеве группы "РОЖДЕСТВО" в 2011 году в Доме офицеров)

Adriano Celentano Любимая песня Челентано (высочайшая энергетика) talentTV


Moscow.media