John

Research Expertise and Interest

nervous system, molecular and cellular mechanisms of olfaction, detection of odors, odorant receptors, olfactory neurons, DNA microarray technologies, genome-wide patterns of gene expression

Research Description

How does the olfactory apparatus of vertebrates detect and discriminate thousands of odors? Our approach to elucidating the mechanisms of olfactory discrimination involves the characterization of odorant receptors and the neural pathways that they activate. We are also interested in the developmental mechanisms responsible for specifying odorant receptor expression in olfactory neurons and the pathfinding of these cells' axons to their appropriate targets. Finally, our lab is developing DNA microarray technologies to elucidate genome-wide patterns of gene expression in the nervous system.

Current Projects

The zebrafish olfactory system. The numerical and anatomical simplicity of the zebrafish olfactory system facilitates an analysis of the molecular and cellular basis of olfactory coding in a vertebrate species. In one line of investigation, we are defining the odorant-binding properties of cloned fish odorant receptors, as fish respond to water soluble cues that are more amenable as probes for biochemical analyses. The zebrafish also offers advantages for studying development; methods for the generation and screening of mutant zebrafish may permit genetic approaches for studying odorant receptor gene expression and olfactory neurogenesis. Genomic mapping of odorant receptor genes and reveals that, as in other vertebrate species, odorant receptor genes are clustered in the zebrafish genome. However, genes tightly linked within a cluster are not coordinately regulated, suggesting that the regulation of individual receptor genes require the interaction of specific trans-acting factors with proximal cis-regulatory sequences. We are pursuing a variety of approaches, including transgenic manipulations, to define the promoter sequences responsible for directing the developmentally-regulated expression of the odorant receptor genes.

Patterning in the olfactory bulb. Olfactory neurons expressing the same odorant receptor converge with great precision to a small number of glomeruli in the olfactory bulb. This suggests that spatial patterns of afferent innervation in the bulb are used to encode olfactory information. What are the mechanisms for specifying the pattern of olfactory neuron projections in the olfactory bulb? We are pursuing several complementary approaches to identify the molecules involved in olfactory axon pathfinding. Transgenic manipulations in the mouse and zebrafish are being used to assess the potential role of candidate genes in the formation of the olfactory sensory map. We are also utilizing DNA microarrays to search for molecules expressedin spatially-restricted patterns in the olfactory bulb; such molecules would be good candidates as guidance cues for ingrowing olfactory axons.

DNA microarrays. Recent advances, which include the sequencing of entire genomes of selected model systems and the ability to survey "genome-wide" patterns of gene expression, now allow the dissection of biological processes at unprecedented levels of detail. We have established in our laboratory the full capabilities for carrying out DNA microarray analysis of gene expression. These techniques allow the analysis of mRNA expression from tens of thousands of genes at a time. To date, we have created high-density cDNA microarrays from the mouse and the zebrafish. We are using these microarrays as tools to investigate patterns of developmentally-regulated and spatially-restricted patterns of gene expression in the vertebrate central nervous system.

Our research is focused on understanding the molecular mechanisms of cellular differentiation in the nervous system. To this end, we are developing and applying DNA microarray-based approaches to identify – on a genome-wide level – the genes and genetic programs that underlie the progression of cells from the undifferentiated stem cell to the mature cell state. The information gained from these studies will be used to interpret and guide future studies on the development of neuronal precursors and mature neurons from human embryonic stem cells. In addition, the expertise of the Functional Genomics Laboratory in DNA microarray approaches and statistical analysis of large-scale gene expression datasets will be made available to all investigators on campus studying human stem cell biology.

In the News

Neuroscientists roll out first comprehensive atlas of brain cells

When you clicked to read this story, a band of cells across the top of your brain sent signals down your spine and out to your hand to tell the muscles in your index finger to press down with just the right amount of pressure to activate your mouse or track pad. A slew of new studies now shows that the area of the brain responsible for initiating this action — the primary motor cortex, which controls movement — has as many as 116 different types of cells that work together to make this happen.

Neuroscientist John Ngai named director of NIH BRAIN Initiative

The National Institutes of Health (NIH) has picked long-time UC Berkeley neuroscientist John Ngai to head its BRAIN Initiative, a multibillion-dollar federal research push to develop new tools that will help scientists understand how the brain works and lead to new treatments for brain dysfunction.

Campus poised to join Obama’s BRAIN initiative

Three UC Berkeley scientists were among a gathering of the nation’s top scientists at the White House this morning (Tuesday, April 2) as President Barack Obama announced a major national initiative to develop new tools to create real-time traffic maps of the human brain.

Featured in the Media

Please note: The views and opinions expressed in these articles are those of the authors and do not necessarily reflect the official policy or positions of UC Berkeley.
February 5, 2020

BRAIN Initiative's first director sets sights on clinical tools

Science
Kelly Servick
The National Institutes of Health has named neuroscience professor John Ngai the first director of their Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative. Professor Ngai's lab studies the neural aspects of our sense of smell, and, funded by the BRAIN initiative, he's led classification studies of the brain's cells using RNA sequencing. Speaking about his anticipated role as director, he says: "How do we leverage all the accomplishments that have been made, not just within BRAIN, but in molecular biology, in engineering, in chemistry and computer science, in data science. The initiative really will benefit from somebody thinking about this 24/7. ... As we learn more about how neural circuits drive behavior ... we can start implementing that knowledge, in terms of treating human diseases. We're seeing progress already in the treatment of certain blinding diseases of the retina. There's at least the amelioration of symptoms of movement disorders. There's a big win in the treatment of spinal muscular atrophy. The therapies right now are extremely expensive, because the patient pool is small, and the risk and investment to develop these tools has been extremely high. I am hopeful that BRAIN, with other efforts in NIH and in partnership with industry, [can] significantly derisk the enterprise and make it more accessible by creating technology platforms that could be applied across multiple disease applications." For more on this, see our press release at Berkeley News.
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