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OU Experts Reflect on 2020 Nobel Prize Recipients for Chemistry, Physics

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October 21, 2020

OU Experts Reflect on 2020 Nobel Prize Recipients for Chemistry, Physics

Nobel Prize recipients represent the minds behind some of humanity’s most significant scientific and cultural accomplishments. In this story, OU researchers share their perspectives on the work by this year’s recipients of the Nobel Prize in Chemistry and the Nobel Prize in Physics.

Chemistry

Emmanuelle Charpentier and Jennifer A. Doudna received the 2020 Nobel Prize in Chemistry for the development of CRISPR, a method for genome editing. The researchers are the first female team to receive this prize and, of the 186 Nobel Prize laureates in Chemistry, they are only the sixth and seventh women to be acknowledged with the award.  

Emmanuelle Charpentier and Jennifer A. Doudna
Nobel Prize in Chemistry: Emmanuelle Charpentier and Jennifer A. Doudna received the 2020 Nobel Prize in Chemistry for the development of CRISPR, a method for genome editing. Image credit: ©Nobel Media. Ill. Niklas Elmehed.

 

Rakhi Rajan, an associate professor of chemistry and biochemistry in the College of Arts and Sciences who also studies CRISPR, shares her thoughts on the significance of this year’s prize.

“History was made when the 2020 Nobel Prize in Chemistry was awarded to two women scientists, Emmanuelle Charpentier (Max Planck Unit for the Science of Pathogens, Berlin, Germany) and Jennifer A. Doudna (University of California, Berkeley, California, USA) for their pioneering work in the development of a genome editing tool using the CRISPR-Cas9 technique,” Rajan said. “Work in their laboratories has enabled the development of CRISPR-Cas9 as a fast and easy method to precisely ‘edit’ any specific location on the genome of a wide range of organisms from bacteria to human cells.”


CRISPR-Cas9

CRISPR-Cas systems are natively found in bacteria and archaea to fight against their viral intruders. Charpentier and Doudna’s laboratories identified the RNA and protein components required for its function.

“They elegantly demonstrated that the RNA component holds the location code that guides the protein Cas9 to the right location in an extensive genome,” Rajan said. “The location specificity solely depends on the complementary base pairing between the ‘guide’ RNA and a stretch of 20 nucleotides in a massive pool of genomic DNA. Cas9 then acts as the genetic scissors to cut that specific position of the genome to make permanent, heritable changes in the code of life.” 

She adds that this mechanism provides the ability to quickly and accurately modify the genomic DNA, forming the basis of a revolutionary technology to edit microorganisms, plants, animals and humans.

“The future of this technology lies in correcting ‘errors’ in human genomes to treat genetically inherited diseases, with several clinical trials currently happening to treat cancer, blood disorders, blindness and viral infections, to name a few,” Rajan said. “Cas9 also has laid its marks on agriculture and animal husbandry, positively impacting future food production.”

At OU, Rajan’s lab is also working on CRISPR research.

 

crispr-cas9

 

“CRISPR-Cas, as it occurs natively, is not error-proof,” Rajan said. “One of the main issues is that the system is not stringent enough, meaning complete complementarity between the RNA and DNA along the entire 20 nucleotide region is not always required to cleave the target DNA.

“While this ‘freedom of error’ is advantageous from a bacterial perspective to cleave intruding viruses with mismatches to offer wider protection, it is undesirable in a gene editing context,” she added. “This activity, called ‘off-target DNA cleavage,’ has to be eliminated for the safe use of this technology in human therapeutics.” Current efforts in the Rajan lab focus on creating protein variants devoid of this off-target cleavage.

CRISPR has been criticized for ethical and social concerns, particularly in regard to genome editing in which edited traits would be passed down as inherited traits.

Another question the lab is addressing is whether Cas9 can cleave DNA in the absence of RNA, which is detrimental to the integrity of the genome. In 2017, Rajan’s lab first established this finding. Since then, another laboratory has also shown that guide-free Cas9 can cause DNA damage in human cells, which warrants further caution in the wide-scale use of this technology for human therapeutics.

Rajan’s lab is currently working toward testing protein variants devoid of this guide-free DNA cleavage for developing safer gene editing tools. Other research aspects the OU team are exploring include understanding CRISPR biology from a bacterial perspective regarding how it protects bacteria from intruding viruses.

The Rajan lab collaborates with other CRISPR experts at the University of Southern California and University of North Texas Health Science Center.


Physics

Three scientists received the 2020 Nobel Prize in Physics for their discoveries related to black holes. Roger Penrose, a University of Oxford professor, received half of the prize "for the discovery that black hole formation is a robust prediction of the general theory of relativity." Reinhard Genzel of the Max Planck Institute and University of California, Berkeley, and Andrea Ghez, a professor at the University of California, Los Angeles, shared the other half of the prize "for the discovery of a supermassive compact object at the centre of our galaxy." This recognition makes Ghez only the fourth woman in history to receive the Nobel Prize in Physics and the second to receive the prize, following Donna Strickland in 2018. 

Roger Penrose received half of the Nobel Prize in Physics "for the discovery that black hole formation is a robust prediction of the general theory of relativity." Reinhard Genzel and Andrea Ghez shared the other half of the prize "for the discovery of a supermassive compact object at the centre of our galaxy." Image credit: ©Nobel Media. Ill. Niklas Elmehed.

 

“Acknowledgement of Andrea Gehz as the fourth woman to be awarded a Nobel prize in physics is a start in the change in culture needed to alleviate the systematic bias that women and under-represented people suffer daily," said Karen Leighly, an OU professor of physics and astronomy in the College of Arts and Sciences.

“Gehz and Genzel led independent American and European groups that each sought to determine the origin of the unusual radio-emitting object called Sagittarius A* that lies in the center of the Milky Way galaxy,” Leighly said.

They used infrared observations to image the stars surrounding the object, which Leighly said is necessary because of the extent of gas and dust between Earth and the center of our galaxy so that only “one trillionth of the visual-band light reaches Earth.” Infrared light, however, penetrates dust and gas much more easily.

“The advent of infrared capabilities on the 10-meter Keck telescope allowed Gehz to make the necessary observations,” Leighly said. “Gehz and Genzel independently found that the stars in the immediate vicinity of Sagittarius A* moved much more rapidly than other stars in the center of the galaxy; some of these stars orbit the dark object with a period as small as 15 years. The only plausible explanation was that they are moving in the gravitational potential of a massive central object, a 4.6 million solar-mass black hole.” 

 

Scientists have obtained the first image of a black hole, using Event Horizon Telescope observations of the center of the galaxy M87. Image Credit: Event Horizon Telescope Collaboration

 

“Black holes are inferred to be present in the centers of most massive galaxies in the universe, so they are not uncommon,” Leighly added. “These observations were important because they provided direct observational proof of the existence of black holes.”

Leighly's group at OU researches quasars, the big brothers of the black hole in the center of our galaxy. Hyunseop “Joseph” Choi, a graduate student on Leighly’s research team, published a paper earlier this year describing the discovery of the most powerful wind yet observed in a quasar.

“With velocities up to one-tenth of the speed of light, and kinetic energies comparable to their radiated energy, quasar winds may influence the evolution of their host galaxies,” Leighly said.

Leighly’s team is currently analyzing the first medium-sized samples of quasar wind spectra. They collaborate with researchers at Ohio State University, Western University and Drexel University.