Advisory Board

Dr. Alysson Renato Muotri

The Los Angeles Times article Brain’s Darwin Machine said

Alysson Muotri was looking for brain cells that glow in the dark.
 
With growing frustration, the 31-year-old Brazilian cancer biologist stared through his microscope at slides of brain tissue for any evidence his experiment had succeeded. His eyes ached.
 
Maria Marchetto, 28, took pity on her husband. Let me look, she said. In a darkened room at the Salk Institute for Biological Studies here, she began to scrutinize the tissue samples for firefly flecks of fluorescent light.
 
Together, the couple stalked an elusive sequence of DNA hidden in the heredity of every human cell. The wayward strand appeared to seek out developing brain cells and, like a virus, arbitrarily alter their genetic makeup.
 
In this way, it might be partly responsible for the infinite variety of the mind.

Alysson Renato Muotri, Ph.D. is Fellow at the Fred H. Gage Laboratory of Genetics, Salk Institute for Biological Studies. His main research interest is understanding the formation of brain complexity.
 
The complexity of the human brain permits the development of sophisticated behavioral repertoires, such as language, tool use, self-awareness, symbolic thought, cultural learning and consciousness. From such dynamic complexity emerged extraordinary technological and artistic masterpieces in a relatively short cultural history. Brain complexity has a creative purpose in contrast to others large, but brute, complex systems such as galaxies and their thousands of billions of stars.
 
Brain complexity is the result of millions of years of evolution that equipped neural stem cells in the embryo with the ability to generate every neuron in the brain — an extraordinary example of cellular potency. Understanding what produces neuronal diversification during brain development has been a longstanding challenge for neuroscientists.
 
About half of the nerve cells created in a developing brain have died by the time that brain has formed. It is believed that a process similar to natural selection decides cell life or death. But natural selection requires variation to generate these various cellular properties.
 
Such variation was thought to be generated by protein-coding genes. However, the sequencing of the human genome revealed that genes represent less than 5% of our genome and thus, there is not enough information to generate thousands of neuronal types in the brain. Variation must reside elsewhere. Curiously, around 95% of the biomedical research is currently focused on these 5%, neglecting the 95% of non-coding regions of the genome.
 
The lack of obvious function of these sequences inspired the concept of “junk DNA” to illustrate the idea that such sequences were mere evolutionary remnants from an ancient RNA World. Part of this junk is composed of mobile elements, thought to be intracellular selfish parasites. These “jumping elements” can multiply by a copy-and-paste mechanism, inserting copies in new genomic locations, occasionally changing the expression pattern of nearby genes or even creating new isoforms.
 
The finding that “jumping genes” impact neuronal genomes challenges the dogma that neurons are genetically homogeneous units1. They move in a defined window during neuronal differentiation, changing the genetic information in single neurons. Such strategy contributes to expand the number of functionally distinct neurons that could be produced from a given stem cell gene pool. This characteristic of variety and flexibility may contribute to the uniqueness of an individual brain, even between genetically identical twins. These mobile elements may be part of a conserved core process responsible for evoking facilitated complex non-random phenotypical variation on which selection may act.
 
Alysson coauthored Somatic mosaicism in neuronal precursor cells mediated by L1 retrotransposition, Development of functional human embryonic stem cell-derived neurons in mouse brain, Alternative Splicing Events Identified in Human Embryonic Stem Cells and Neural Progenitors, Photorepair Prevents Ultraviolet-induced Apoptosis in Human Cells Expressing the Marsupial Photolyase Gene, Ribozymes and the anti-gene therapy: how a catalytic RNA can be used to inhibit gene function, and Restoring DNA repair capacity of cells from three distinct diseases by XPD gene-recombinant adenovirus.
 
Alysson earned a BSc in Biological Sciences from the State University of Campinas (Unicamp) and earned his PhD in Biology Genetics from the University of Sao Paulo. Watch his presentation Development of Functional Human Embryonic Stem Cell-Derived Neurons in Mouse Brain at California Institute for Telecommunications and Information Technology’s “Stem Cell Meeting on the Mesa”.