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Combining two powerful technologies, editing genomes using CRISPR and generating mini-brains from stem cells, researcher Alysson R. Muotri intends to clear up one of the issues the most fundamental of the human species: What makes us unique
Dr. Alysson R. Muotri, Ph.D., professor at the Faculty of Medicine and director of the Stem Cell program of the University of California, and co-founder of biotechnology start-up TISMOO, recreated organelles
Cerebral organoids, or mini-brains, are miniaturized cell structures created from stem cells that partly replicate structure and functionality of the brain. develop the human brain. Muotri had already used these mini-brains to unravel the genetic contribution of autism and other neurological diseases, and to test new drugs. In collaboration with Brazilian colleagues, Muotri also used mini-brains to show the causal relationship between the Zika virus and the microcephaly epidemic in Brazil in 2015.
Now, using a new version of mini-brains functional brains capable of generating sophisticated Neotropic networks .
"In the past, we have already compared human minibrows with other primates, such as the chimpanzee. However, in order to understand the origins of the modern brain, we would need to compare them with the mini-brains of our closest evolutionary cousins, such as Neanderthals. "
Neanderthals
Modern humans and Neanderthals split into two lineages 400,000 years ago. Our ancestors stayed in Africa, while Neanderthals migrated to Northern Europe. About 60,000 years ago, archaeological remains suggest that our ancestors eventually left Africa for Europe. It is at this point that both species coexisted. Recent genetic evidence shows that both groups have had bad, but the nature of these encounters is still a mystery. The fact is that the Neanderthals finished shortly after this contact with our species and the causes of this extinction are still a reason for much speculation.
Today, all that we know of Neanderthals comes from the study of fossils and archaeological sites. Evidence has shown that Neanderthals used to bury the dead and produce rudimentary tools and ornaments, suggesting an abstract and symbolic thought. Even artistic evidence has been attributed to Neanderthals, but this remains controversial. From a neurological point of view, they are known to have a slightly larger brain than modern humans, with some structural differences.
The discovery
The genetic material of these ancient humans, also extracted was decoded in 2010. Comparing the genome of Neanderthals with those of modern humans, several differences were noted. Some regions of the genome still exist in the current population, while other fragments have been eliminated by natural selection, perhaps because of certain adaptive disadvantages in health, fertility, appearance or cognition
"Our group used genomic tools to align genomes. Neanderthals are discovering which genes would be unique and no longer present in the human populations of today. We then selected active genes during neural development and related to neurological diseases. We use this information to modify the genome of human stem cells and then create Neanderthal mini-brains, "says Muotri.
The results are impressive. During the examination of gene expression during neurodevelopment, the group noticed significant changes between the Neanderthal and human mini-brains. At the cellular level, the changes were even more distinct: changes in migratory patterns of progenitor cells led to the formation of distinct globular structures in the Neanderthal mini-brains. The results of this research will be presented for the first time at an international symposium organized by CARTA () whose results will be presented for the first time at an international symposium organized by CARTA (). Center for Academic Research and Training in Anthropogeny ), California: https://carta.anthropogeny.org/events/imagination-and-human-origins . The context of the symposium focuses on the human imagination and Muotri believes that demonstrating the differences between humans and the Neanderthal minicellular can explain our unique cognitive ability.
"The imagination is one of the most important and complex mechanisms in the history of humanity." The imagination is inherent in the modern human brain, we spend a lot of time to imagine things.We imagine situations of a child (a monster under the bed, a fictitious friend) at adulthood (we imagine our future, everyday situations). Imagination allows us to dream, to create technology and to achieve our goals.Image is power.It is a fantastic evolutionary tool, "says professor and researcher [19659005] The study of Muotri also comes up against ethical problems because all the mini-brains used are capable of electrical activity similar to that of a newborn. Recently, a group of scientists and ethicists published an article in the Journal Nature asking for regulation of these questions: How should the brain organoids of Muotri be treated?
Aside from the ethical issues, it is clear that results obtained with Neanderthal brain organoids may reveal details about the cognitive capacity that has resulted in the success of the modern human species and at the same time. ;failure. Neanderthal evolution.
About Dr. Alysson R. Muotri
Dr. Alysson Renato Muotri is Professor at the Faculty of Medicine and Director of the Institute of Stem Cells at the University of California. The researcher is also a founding partner of TISMOO, the first biotechnology company to use genomic information and functional mini-brains to develop new treatments for autism spectrum disorders (ASD). Muotri is still one of the most internationally recognized Brazilian scientists, with the largest number of publications in high impact journals. A graduate in biology from UNICAMP, he holds a Ph.D. in genetics from the USP. In 2002, he was hired by the Salk Institute for Biological Research for a post-doctorate in neuroscience and stem cells. In 2008, he became principal investigator for a research group at the University of California, where he works until today. During this trajectory, Muotri collects international awards such as the prestigious new innovator Awar from the NIH director, NARSAD, EUREKA, Surugadai, among others.
About TISMOO
Created in 2015, the biotechnology startup TISMOO is the first laboratory in the world exclusively dedicated to genetic badyzes centered on personalized therapeutic perspectives for the Autism spectrum disorder and other neurological disorders of genetic origin, such as Rett syndrome, CDKL5, Timothy syndrome, Fragile X syndrome of Angelman syndrome and Phelan-McDermid. With renowned scientists in his team, the goal of TISMOO is to recreate neural developmental stages from the patient's own cells – mini-brains – to capture each individual's genetic material in order to study how their mutations lead to a specific clinical picture and look for new ways to reverse the process with pharmacological treatments, improving the quality of life of patients and families with neurological diseases. Since 2017, TISMOO is also established in the United States in collaboration with other laboratories in the country. Suggestion for consultation for journalists :
Dra. Patrícia Beltrão-Braga, Institute of Biosciences of the USP, [email protected]
Dra. Beltrão-Braga is an expert in creating mini-brains for research.
Dr. Walter Neves, USP Institute of Biology, Laboratory for Studies in Human Evolution
Dr. Neves is an anthropologist and archaeologist, known for the morphological badysis of early humans in South America.
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