Editing
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Editing Parkinson's Disease – KAIST Makes World's First Discovery of an Inflammatory RNA Editing Enzyme
< Professor Minee Choi of the Department of Brain and Cognitive Sciences (top left). Professor Sonia Gandhi (top right) and Professor Klenerman of the University College London (bottom right) >
Parkinson's disease (PD) is a neurodegenerative disorder in which the α-synuclein protein abnormally aggregates within brain cells, causing neuronal damage. Through international collaboration, researchers at KAIST have revealed that RNA editing plays a crucial role in regulating neuroinflammation, a key pathology of Parkinson's disease.
KAIST (represented by President Kwang-Hyung Lee) announced on the 27th of April that a research team led by Professor Minee L. Choi from the Department of Brain and Cognitive Sciences, in collaboration with University College London (UCL) and the Francis Crick Institute, discovered that the RNA editing enzyme ADAR1 plays an important role in controlling immune responses in astrocytes, glial cells that trigger protective reactions in the brain, and demonstrated that this mechanism is critically involved in the progression of Parkinson’s disease.
Professor Choi's research team created a co-culture model composed of astrocytes and neurons derived from stem cells originating from Parkinson's disease patients, in order to study the inflammatory responses of brain immune cells. They then treated the model with α-synuclein aggregates, which are known to cause Parkinson’s disease, and analyzed how the immune cells' inflammatory responses changed.
< Figure 1. Schematic diagram of the inflammatory RNA editing model in Parkinson's disease >
As a result, it was found that early pathological forms of α-synuclein, known as oligomers, activated the Toll-like receptor pathway, which acts as a danger sensor in astrocytes, as well as the interferon response pathway, an immune signaling network that combats viruses and pathogens. During this process, the RNA editing enzyme ADAR1 was expressed and transformed into an isoform with an altered protein structure and function.
Notably, the RNA editing activity of ADAR1, which normally functions to regulate immune responses during viral infections by converting adenosine (A) to inosine (I) through a process known as A-to-I RNA editing, was found to be abnormally focused on genes that cause inflammation rather than operating under normal conditions. This phenomenon was observed not only in the patient-derived neuron models but also in postmortem brain tissues from actual Parkinson’s disease patients.
< Figure 2. Experimental design and inflammatory response induction in astrocytes following treatment with α-synuclein oligomers (abnormally folded protein fragments) >
This directly proves that the dysregulation of RNA editing induces chronic inflammatory responses in astrocytes, ultimately leading to neuronal toxicity and pathological progression.
This study is significant in that it newly identified the regulation of RNA editing within astrocytes as a key mechanism behind neuroinflammatory responses. In particular, it suggests that ADAR1 could serve as a novel genetic target for the treatment of Parkinson’s disease.
It is also noteworthy that the study reflected actual pathological characteristics of patients by utilizing patient-specific induced pluripotent stem cell-based precision models for brain diseases.
Professor Minee L. Choi stated, “This study demonstrates that the regulator of inflammation caused by protein aggregation operates at the new layer of RNA editing, offering a completely different therapeutic strategy from existing approaches to Parkinson's disease treatment." She further emphasized, “RNA editing technology could become an important turning point in the development of therapeutics for neuroinflammation.”
< Figure 3. When treated with α-synuclein oligomers, the causative agent of Parkinson's disease, A-to-I RNA editing is induced to change genetic information by ADAR in patient-derived stem cell-differentiated glial cells, confirming that α-synuclein is likely to be associated with the progression of Parkinson's disease through RNA editing >
This study was published in Science Advances on April 11, with Professor Choi listed as a co-first author.
Paper Title: Astrocytic RNA editing regulates the host immune response to alpha-synuclein, Science Advances Vol.11, Issue 15. (DOI:10.1126/sciadv.adp8504)
Lead Authors: Karishma D’Sa (UCL, Co-First Author), Minee L. Choi (KAIST, Co-First Author), Mina Ryten (UCL, Corresponding Author), Sonia Gandhi (Francis Crick Institute, University of Cambridge, Corresponding Author)
This research was supported by the Brain Research Program and the Excellent Young Researcher Program of the National Research Foundation of Korea, as well as KAIST’s Daekyo Cognitive Enhancement Program.
2025.05.02 View 348 -
Life After COVID-19: Big Questions on Medical and Bio-Engineering
KAIST GSI forum explores big questions in the medical and bio-engineering revolution caused by the COVID-19 in fight against infectious diseases and life quality
On September 9, the Global Strategy Institute at KAIST will delve into innovative future strategies for the medical and bio-engineering sectors that have been disrupted by COVID-19. The forum will live stream via YouTube, KTV, and Naver TV from 9:00 am Korean time.
The online forum features a speaker lineup of world-renowned scholars who will discuss an array of bio-engineering technologies that will improve our quality of life and even extend our life span. This is the GSI’s third online forum since the first one in April that covered the socio-economic implications of the global pandemic and the second one in June focusing on the education sector.
In hosting the third round of the GSI Forum series, KAIST President Sung-Chul Shin stressed the power of science and technology saying, “In this world full of uncertainties, one thing for sure is that only the advancement of science and technology will deliver us from this crisis.” Korean Prime Minister Sye-Kyun Chung will also deliver a speech explaining the government’s response to COVID-19 and vaccine development strategies.
The President of the National Academy of Medicine in the US will share ideal policies to back up the bio-engineering and medical sectors and Futurist Thomas Frey from the Davinci Institute will present his distinct perspectives on our future lives after COVID-19. His thought-provoking insights on advancements in the bioengineering sector will examine whether humanity can put an end to infectious diseases and find new ways to lengthen our lives.
Two distinguished professors in the field of genetic engineering technology will share their latest breakthroughs. Professor George McDonald Church from Harvard Medical School who developed genome sequencing will deliver a keynote speech on how the advancement of gene editing and genome technology will overcome diseases and contribute to extending human life spans.
Professor Kwang-Soo Kim, a KAIST alumnus from Harvard Medical School who recently reported new discoveries for Parkinson’s disease treatment by reprogramming a patient’s own skin cells to replace cells in the brain, will introduce the latest clinical cell treatment technologies based on personalized therapeutics.
Senior Vice President and Chief Product Officer of Illumina Susan Tousi, a leading genome sequencing solution provider, will describe genome analysis technology and explore the potential for disease prevention.
KAIST medical scientist Jeong Ho Lee, who was the first to identify the causes of intractable epilepsies and has identified the genes responsible for several developmental brain disorders. Professor Jin-Hyung Lee from Stanford University and Dr. David B. Resnik from the National Institute of Environmental Health Science will also join the speaker lineup to discuss genetics-based personalized solutions to extend human life spans.
The forum will also invite about 50 young scientists and medical researchers from around the world to participate in an online panel session. They will engage in a Q&A session and a discussion with the speakers.
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2020.09.04 View 10570 -
KAIST's Advanced Biomass R&D Center and ToolGen will cooperate
The Advanced Biomass R&D Center (ABC) at KAIST and ToolGen, Inc., a Korean biotechnology company focused on the development of engineered nucleases that can be used as essential tools for editing genetic information in microbial, plant, animal, and human cells, signed a memorandum of understanding (MOU) on August 18, 2014 for technology exchange and research collaboration.
ABC is headed by Executive Director Ji-Won Yang, a professor emeritus at the Department of Chemical and Biomolecular Engineering, and Chief Executive Officer Jong-Moon Kim for ToolGen.
The newly signed MOU encourages collaborations in the following areas:
- Development of genome editing technology for microalgae modification
- Development of microalgae that increases biofuel production through the
application of genome editing technology
- Creation of education and training programs for researchers
- Collaboration in other areas
In addition, the two organizations decided to cooperate in the improvement of biofuel yields using ToolGen’s genome editing technology, the commercialization of research outcomes, and the development of eco-friendly biofuels from biomass.
Executive Director Yang commented that “improving biofuel production is crucial to accelerate the commercialization of biofuels, and collaborating with ToolGen will help us realize that goal.” He further said that “The importance of this MOU lies in the fact that the global chemical industry including Korea has been making substantial efforts to shift its attention from a fossil fuel-based development to a more bio-based technology.”
Jin-Soo Kim, the director of the Genome Editing Research Center at the Institute of Basic Sciences in Korea and the cofounder of ToolGen, added that “ToolGen has successfully commercialized its third generation genetic scissors, which shows a lot of promise for commercialization. Our collaboration with KAIST will serve as the driving force to create new industries and accordingly, new jobs.”
2014.09.03 View 10983 -
Professor Sang-Yup Lee Senior Editor of U.S. Biotechnology Journal
Professor Sang-Yup Lee Named Senior Editor of U.S. Biotechnology Journal
Will supervise paper examination in the fields of system biology, system bioengineering and
metabolic engineering, and set editing direction
Professor Sang-Yup Lee, LG Chemical’s Chair-Professor and the leader of BK project group of KAIST Chemical and Biomolecular Engineering Department, was named senior editor of Biotechnology Journal published by the U.S. Wiley-VCH.
Professor Lee will supervise paper examination in the fields of system biology, system bioengineering and metabolic engineering, and set and manage the editing direction of the journal.
‘Biotechnology Journal’ was first published in January 2006 to exchange rapidly-exchanging knowledge and information in life science and its relevant fields by Wiley, a world-famous science journal publisher with the history of 208 years (founded in 1799). Particularly, ‘Biotechnology Journal’ is a new-typed scientific journal treating various fields such as life science research-relevant ethics and cultures necessary for general people as well as expertise research information of life science.
“Although taking charge of editing of many scientific journals spends much time, it’s very fruitful that I’ll lead the direction of research papers of many world-famous scientific journals and I can make efforts to prevent outstanding papers by Korean scientists from being disadvantaged,” said Professor Lee.
“More Korean scholars are taking charge of editing jobs of world-famous scientific journals. It’s a good indication that the capacities of Korean science and engineering have been enhanced significantly as much,” a staff of KAIST PR team said.
Meanwhile, Professor Lee, distinguished by outstanding research performances in the fields of metabolic engineering and system life engineering, is now ▲associate editor of Biotechnology and Bioengineering, top scientific journal of biotech engineering published by the U.S. Wiley ▲editor of Applied Microbiology and Biotechnology published by German Springer ▲ associate editor of Bioprocess and Biosystems Engineering by German Springer, and editing member of ▲ Journal of Bioinformatics and Computational Biology by Singapore’s World Scientific ▲ Asia Pacific Biotech News ▲ Biochemical Engineering Journal, Metabolic Engineering, and Microbial Cell Factory by Elsevier.
2007.02.02 View 15923