In the paper, published November 22 as an online-first publication in the journal Genes, Brain and Behavior, the researchers identified the hierarchical tree of CGG–TF networks that determine the patterns of genes expressed during brain development and found that some “master transcription factors” at the top level of the hierarchy regulated the expression of a significant number of gene groups.
Instead of a taking the approach that a single gene creates a single response, researchers used contemporary methods of data analysis, along with the Gordon supercomputer at the university’s San Diego Supercomputer Center (SDSC), to identify CGGs responsible for brain development which can be affected for treatment of mental disorders. The team found that these groups of genes act in concert to send signals at various levels of the hierarchy to other groups of genes, which control the general and more specific (depending of the level) events in brain structure development.
“We have proposed a novel, though still hypothetical, strategy of drug design based on this hierarchical network of TFs that could pave the way for a new category of pharmacological agents that could be used to block a pathway at a critical time during brain development as an effective way to treat and even prevent mental disorders such as ASD and schizophrenia,” said lead author Igor Tsigelny, a research scientist with SDSC, as well as the university’s Moores Cancer Center and Department of Neurosciences. “On a broader scale, these findings have the potential to change the paradigm of drug design.”
Using samples taken from three different regions of the brains of rats, the researchers used Gordon and SDSC’s BiologicalNetworks server to conduct numerous levels of analysis, starting with processing of microarray data and SOM (self-organizing maps) clustering, before determining which gene zones were associated with significant developmental changes and brain disorders.
Researchers then conducted analyses of stages of development and quick comparisons between rat and human brain development, in addition to pathway analyses and functional and hierarchical network analyses. The team then analyzed specific gene–TF interactions, with a focus on neurological disorders, before investigating further directions for drug design based on analysis of the hierarchical networks.
Tsigelny’s collaborators included Valentina L. Kouzentsova (SDSC and Moores), Michael Baitaluk (SDSC); and Jean-Pierre Changeux, with the Institut Pasteur, in Paris, France. Changeux also is a Skaggs distinguished visiting professor in pharmacology at UC San Diego (2008) and a member of the foreign faculty at UC San Diego’s Kavli Institute for Brain and Mind. In addition to SDSC and its computational resources, support for the research paper, called A Hierarchical Coherent-Gene-Group Model for Brain Development, was provided by National Institutes of Health grant # GM084881 for Baitaluk.
Jan Zverina | Newswise Science News
Unique brain 'fingerprint' can predict drug effectiveness
11.07.2018 | McGill University
Direct conversion of non-neuronal cells into nerve cells
03.07.2018 | Universitätsmedizin der Johannes Gutenberg-Universität Mainz
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.
Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
17.07.2018 | Information Technology
17.07.2018 | Materials Sciences
17.07.2018 | Power and Electrical Engineering