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Posts Tagged ‘Jennifer Doudna’


Jennifer Doudna, Woman of Science Award

Larry H. Bernstein, MD, FCAP, Curator

LPBI

Jennifer Doudna, Ph.D., one of the brains behind the revolutionary CRISPR-Cas9 gene editing technology, started out as a self-proclaimed “nerdy, geeky type” who loved math and tried to figure out how the world works by performing experiments.

Doudna, along with five other outstanding Laureates, will be honored on March 24 for her groundbreaking work, with the L’Oreal-UNESCO For Women in Science Award in Paris.  Doudna, professor in the department of molecular and cell biology at the University of California, Berkeley and an investigator at the Howard Hughes Medical Institute, told Bioscience Technology about her early exploration into science and where she thinks CRISPR will have the biggest impact.

Before becoming a renowned scientist, Dounda was a curious kid interested in discovery. Her first introduction to biochemistry came in middle school, when her father gave her James Watson’s The Double Helix. “When I picked it up, I couldn’t put it down,” she told Bioscience Technology. “A high school chemistry class cemented my determination to become a scientist.”

During her time at Hilo High in Hawaii her interest was stoked further by a presentation from a woman from the University of Hawaii who detailed processes that took place at the molecular level and how normal cells became cancerous.

“I was just dumbstruck and so fascinated by her work,” Doudna said.  “I said to myself ‘that’s exactly what I want to do, I want to be her.’”

Doudna said she got some lab time under her belt, working at a family friend’s lab over the summer collecting samples and embedding them in resins, then examining thin slices under an electron microscope.  “I was captivated by it – looked forward to going in every day,” she said.  “I was always thinking, ‘I’m going to uncover a mystery today!’” Doudan said she credits her various experiences in Hilo with the choices that eventually led to her career.

That love of discovery is something she wants to point out to postdoctoral or younger scientists – that science is about asking questions.  She cautions, though, that one then has to be patient while figuring out the answers to questions, and to “pay attention to little details that might be unexpected in one’s research.”

Doudna, a highly accomplished scientist herself sees opportunities improving for women in STEM.  “The more women we invite into the field of science and support, the more this will change. L’Oreal-UNESCO’s For Women in Science program is doing amazing work in terms of encouraging women to pursue STEM— it’s about creating an environment that celebrates and supports the important work women in science are doing.”

CRISPR’s far-reaching implications

CRISPR, which acts like molecular scissors, is a relatively simple way to modify an organism’s DNA. It has tremendous potential, from treating and curing diseases, to agricultural uses for tweaking food.

The potential uses of CRISPR are great, but in the medium term Doudna said she thinks that we’re going to see CRISPR-Cas9 technology used to repair mutations that are well-known to cause genetic diseases, like sickle-cell anemia and other blood disorders.

“We have a pretty good idea about how we could actually introduce the Cas9 protein and its guiding RNA into those cells to create the changes that are necessary for therapeutic benefit,” she said.

In the longer term, Doudna hopes to see the technology applied to other types of genetic diseases such as diseases of the liver, the lung, and cystic fibrosis.

“Duchenne muscular dystrophy is caused by a genetic mutation, in which the mutations have been known for a while, but we have not had, until now, an effective tool to employ for correcting them.”

While CRISPR has many exciting potential applications, the new technology also comes with many ethical concerns, such as germline editing, where traits are passed down to the next generation.  Some worry that this could lead to designer babies whose genome has been edited not for disease prevention but for things like intelligence or physical traits — and Doudna has led the charge in asking scientists to consider and weigh ethical considerations.  In December a group of international scientists convened at a meeting where they called for a moratorium on making inheritable changes to the human genome.

“Science is global, and countries across the world have different perspectives on how to use CRISPR,” Doudna said.  “This is why we’ve called for a moratorium on its use, as I had a growing sense that there were profound ethical concerns where genetic changes in embryos are put into future generations.”

Doudna said she also believes that scientists should be better prepared to think about and shape the societal, ethical and ecological consequences of their work.  “Providing biology students with some training about how to discuss science with non-scientists could be transformative.”

The fame that came with the development of CRISPR has been a surprise to Doudna, but she said she’s very grateful for the attention it brings to gene editing.

“Being honored by programs such as L’Oreal-UNESCO’s For Women in Science is not just about receiving a grant or title, but it’s a privilege to be amongst a very strong group of incredibly smart and accomplished female scientists.”

Another U.S.-based scientist, postdoctoral astrophysics researcher Sabrina Steirwalt, Ph.D., from the University of Virginia, will also be honored at the event as an International Rising Talent for her work on the study of how galaxies evolve.

After being nominated by others in the field, the five 2016 Laureates were selected by an independent and international jury of scientists, and each will receive 100,000 euros.

 

Other related articles on CRISPR published in this Open Access Online Scientific Journal include the following:

  • Status “Interference — Initial memorandum” – CRISPR/Cas9 – The Biotech Patent Fight of the Century: UC, Berkeley and Broad Institute @MIT

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/01/06/status-interference-initial-memorandum-crisprcas9-the-biotech-patent-fight-of-the-century/

 

  • UPDATED – Medical Interpretation of the Genomics Frontier – CRISPR – Cas9:  Gene Editing Technology for New Therapeutics

Authors and Curators: Larry H Bernstein, MD, FCAP and Stephen J Williams, PhD and Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2015/09/07/medical-interpretation-of-the-genomics-frontier-crispr-cas9-gene-editing-technology-for-new-therapeutics/

 

  • 67 articles on CRISPR in PharmaceuticalIntelligence.com

https://pharmaceuticalintelligence.com/category/crisprcas9-gene-editing/

 

Nine Parties had come forward: Opposition Procedure to the Broad Institute’s first European CRISPR–Cas9 Patent

Lab Management: About The Doudna Lab, RNA Biology at UC Berkeley, HHMI

Jennifer Doudna, cosmology teams named 2015 Breakthrough Prize winners

Annual Margaret Pittman Lecture, honors the NIH’s first female lab chief, March 11, 2015, 3:00:00 PM by Jennifer Doudna, Ph.D., University of California, Berkeley

2:15 – 2:45, 6/13/2014, Jennifer Doudna “The biology of CRISPRs: from genome defense to genetic engineering”

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Ribozymes and RNA Machines –  Work of Jennifer A. Doudna

Reporter: Aviva Lev-Ari, PhD, RN

 

UPDATED 3/27/2014

New DNA-editing technology spawns bold UC initiative

http://newscenter.berkeley.edu/2014/03/18/new-dna-editing-technology-spawns-bold-uc-initiative/

Crispr Goes Global

http://vcresearch.berkeley.edu/news/profile/doudna_jennifer

UPDATED 3/5/2014

Double Nicking by RNA-Guided CRISPR Cas9 for Enhanced Genome Editing Specificity

http://www.cell.com/retrieve/pii/S0092867413010155

One-Step Generation of Mice Carrying Mutations in Multiple Genes by CRISPR/Cas-Mediated Genome Engineering

http://www.cell.com/retrieve/pii/S0092867413004674

RNA-Guided Human Genome Engineering via Cas9

http://www.sciencemag.org/content/suppl/2013/01/03/science.1232033.DC1

SOURCE

From: Expert CRISPR/Cas9 Publications <Expert_CRISPRCas9_Publications@mail.vresp.com>
Date: Tue, 04 Mar 2014 17:03:01 +0000
To: <avivalev-ari@alum.berkeley.edu>
Subject: CRISPR-mediated gene editing resources

 

UPDATED on 11/10/2013

Exclusive: ‘Jaw-dropping’ breakthrough hailed as landmark in fight against hereditary diseases as Crispr technique heralds genetic revolution

Development to revolutionise study and treatment of a range of diseases from cancer, incurable viruses such as HIV to inherited genetic disorders such as sickle-cell anaemia and Huntington’s disease

SCIENCE EDITOR

Thursday 07 November 2013

A breakthrough in genetics – described as “jaw-dropping” by one Nobel scientist – has created intense excitement among DNA experts around the world who believe the discovery will transform their ability to edit the genomes of all living organisms, including humans.

Click image above to enlarge graphic

The development has been hailed as a milestone in medical science because it promises to revolutionise the study and treatment of a range of diseases, from cancer and incurable viruses to inherited genetic disorders such as sickle-cell anaemia and Down syndrome.

For the first time, scientists are able to engineer any part of the human genome with extreme precision using a revolutionary new technique called Crispr, which has been likened to editing the individual letters on any chosen page of an encyclopedia without creating spelling mistakes. The landmark development means it is now possible to make the most accurate and detailed alterations to any specific position on the DNA of the 23 pairs of human chromosomes without introducing unintended mutations or flaws, scientists said.

The technique is so accurate that scientists believe it will soon be used in gene-therapy trials on humans to treat incurable viruses such as HIV or currently untreatable genetic disorders such as Huntington’s disease. It might also be used controversially to correct gene defects in human IVF embryos, scientists said.

Until now, gene therapy has had largely to rely on highly inaccurate methods of editing the genome, often involving modified viruses that insert DNA at random into the genome – considered too risky for many patients.

The new method, however, transforms genetic engineering because it is simple and easy to edit any desired part of the DNA molecule, right down to the individual chemical building-blocks or nucleotides that make up the genetic alphabet, researchers said.

“Crispr is absolutely huge. It’s incredibly powerful and it has many applications, from agriculture to potential gene therapy in humans,” said Craig Mello of the University of Massachusetts Medical School, who shared the 2006 Nobel Prize for medicine for a previous genetic discovery called RNA interference.

“This is really a triumph of basic science and in many ways it’s better than RNA interference. It’s a tremendous breakthrough with huge implications for molecular genetics. It’s a real game-changer,” Professor Mello told The Independent.

“It’s one of those things that you have to see to believe. I read the scientific papers like everyone else but when I saw it working in my own lab, my jaw dropped. A total novice in my lab got it to work,” Professor Mello said.

In addition to engineering the genes of plants and animals, which could accelerate the development of GM crops and livestock, the Crispr technique dramatically “lowers the threshold” for carrying out “germline” gene therapy on human IVF embryos, Professor Mello added.

The new method of gene therapy makes it simple and easy to edit any desired part of the DNA molecule (Getty Creative)

The new method of gene therapy makes it simple and easy to edit any desired part of the DNA molecule (Getty Creative) Germline gene therapy on sperm, eggs or embryos to eliminate inherited diseases alters the DNA of all subsequent generations, but fears over its safety, and the prospect of so-called “designer babies”, has led to it being made illegal in Britain and many other countries.

The new gene-editing technique could address many of the safety concerns because it is so accurate. Some scientists now believe it is only a matter of time before IVF doctors suggest that it could be used to eliminate genetic diseases from affected families by changing an embryo’s DNA before implanting it into the womb.

“If this new technique succeeds in allowing perfectly targeted correction of abnormal genes, eliminating safety concerns, then the exciting prospect is that treatments could be developed and applied to the germline, ridding families and all their descendants of devastating inherited disorders,” said Dagan Wells, an IVF scientist at Oxford University.

“It would be difficult to argue against using it if it can be shown to be as safe, reliable and effective as it appears to be. Who would condemn a child to terrible suffering and perhaps an early death when a therapy exists, capable of repairing the problem?” Dr Wells said.

The Crispr process was first identified as a natural immune defence used by bacteria against invading viruses. Last year, however, scientists led by Jennifer Doudna at the University of California, Berkeley, published a seminal study showing that Crispr can be used to target any region of a genome with extreme precision with the aid of a DNA-cutting enzyme called CAS9.

Since then, several teams of scientists showed that the Crispr-CAS9 system used by Professor Doudna could be adapted to work on a range of life forms, from plants and nematode worms to fruit flies and laboratory mice.

Earlier this year, several teams of scientists demonstrated that it can also be used accurately to engineer the DNA of mouse embryos and even human stem cells grown in culture. Geneticists were astounded by how easy, accurate and effective it is at altering the genetic code of any life form – and they immediately realised the therapeutic potential for medicine.

“The efficiency and ease of use is completely unprecedented. I’m jumping out of my skin with excitement,” said George Church, a geneticist at Harvard University who led one of the teams that used Crispr to edit the human genome for the first time.

“The new technology should permit alterations of serious genetic disorders. This could be done, in principle, at any stage of development from sperm and egg cells and IVF embryos up to the irreversible stages of the disease,” Professor Church said.

David Adams, a DNA scientist at the Wellcome Trust Sanger Institute in Cambridge, said that the technique has the potential to transform the way scientists are able to manipulate the genes of all living organisms, especially patients with inherited diseases, cancer or lifelong HIV infection.

“This is the first time we’ve been able to edit the genome efficiently and precisely and at a scale that means individual patient mutations can be corrected,” Dr Adams said.

“There have been other technologies for editing the genome but they all leave a ‘scar’ behind or foreign DNA in the genome. This leaves no scars behind and you can change the individual nucleotides of DNA – the ‘letters’ of the genetic textbook – without any other unwanted changes,” he said.

Timeline: Landmarks in DNA science

Restriction enzymes: allowed scientists to cut the DNA molecule at or near a recognised genetic sequence. The enzymes work well in microbes but are more difficult to target in the more complex genomes of plants and animals. Their discovery in the 1970s opened the way for the age of genetic engineering, from GM crops to GM animals, and led to the 1978 Nobel Prize for medicine.

Polymerase chain reaction (PCR): a technique developed in 1983 by Kary Mullis (below, credit: Getty) in California allowed scientists to amplify the smallest amounts of DNA – down to a single molecule – to virtually unlimited quantities. It quickly became a standard technique, especially in forensic science, where it is used routinely in analysing the smallest tissue samples left at crime scenes. Many historical crimes have since been solved with the help of the PCR test. Mullis won the Nobel Prize for chemistry in 1993.

RNA interference: scientists working on the changing colour of petunia plants first noticed this phenomenon, which was later shown to involve RNA, a molecular cousin to DNA. In 1998, Craig Mello and Andrew Fire in the US demonstrated the phenomenon on nematode worms, showing that small strands of RNA could be used to turn down the activity of genes, rather like a dimmer switch. They shared the 2006 Nobel Prize for physiology or medicine for the discovery.

Zinc fingers: complex proteins called zinc fingers, first used on mice in 1994, can cut DNA at selected sites in the genome, with the help of enzymes. Another DNA-cutting technique called Talens can do something similar. But both are cumbersome to use and difficult to operate in practice – unlike the Crispr technique.

VIEW VIDEO

http://www.independent.co.uk/news/science/indyplus-video-crispr-technique-8925604.html

a video of how the Crispr system derived from bacteria works on human cells to correct genetic defects

SOURCE

http://www.independent.co.uk/news/science/exclusive-jawdropping-breakthrough-hailed-as-landmark-in-fight-against-hereditary-diseases-as-crispr-technique-heralds-genetic-revolution-8925295.html?goback=%2Egde_2106240_member_5804987154979381248#%21

Jennifer A. Doudna

Professor of Chemistry
Professor of Biochemistry & Molecular Biology

email: doudna@berkeley.edu
office: 708A Stanley Hall
phone: 510-643-0225
fax: 510-643-0008

lab: 731 Stanley Hall
lab phone: 510-643-0113
lab fax: 510-643-0080

Research Group URL
Recent Publications

Research Interests

Chemical Biology

Ribozymes and RNA Machines: RNA forms a variety of complex globular structures, some of which function like enzymes or form functional complexes with proteins. There are three major areas of focus in the lab: catalytic RNA, the function of RNA in the signal recognition particle and the mechanism of RNA-mediated internal initiation of protein synthesis. We are interested in understanding and comparing catalytic strategies used by RNA to those of protein enzymes, focusing on self-splicing introns and the self-cleaving RNA from hepatitis delta virus (HDV), a human pathogen. We are also investigating RNA-mediated initiation of protein synthesis, focusing on the internal ribosome entry site (IRES) RNA from Hepatitis C virus. Cryo-EM, x-ray crystallography and biochemical experiments are focused on understanding the structure and mechanism of the IRES and its amazing ability to hijack the mammalian ribosome and associated translation factors. A third area of focus in the lab is the signal recognition particle, which contains a highly conserved RNA required for targeting proteins for export out of cells. Each of these projects seeks to understand the molecular basis for RNA function, using a combination of structural, biophysical and biochemical approaches.

Biography

Medical School, 1989-1991; Post-doctoral fellow, University of Colorado, 1991-1994; Assistant/Associate professor, (1994-1998), Professor, (1999-2001), Yale University. Professor of Biochemistry & Molecular Biology, UC Berkeley, (2002-). Howard Hughes Medical Investigator 1997 to present. Packard Foundation Fellow Award, 1996; NSF Alan T. Waterman Award, 2000. Member, National Academy of Sciences, 2002. Member, American Academy of Arts and Sciences, 2003; American Association for the Advancement of Science Fellow Award, 2008; Member, Institute of Medicine of the National Academies, 2010.

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Diagnosing Diseases & Gene Therapy: Precision Genome Editing and Cost-effective microRNA Profiling

https://pharmaceuticalintelligence.com/2013/03/28/diagnosing-diseases-gene-therapy-precision-genome-editing-and-cost-effective-microrna-profiling/

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