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Oliver Hobert Named Javits Neuroscience Investigator

Oliver Hobert
Oliver Hobert

Oliver Hobert, an interdisciplinary faculty member of the Department of Systems Biology, has received a Javits Neuroscience Investigator Award from the National Institute of Neurological Disorders and Stroke (NINDS). This prestigious grant provides long-term support for investigators who have demonstrated exceptional achievement throughout their careers. The award will enable the Hobert Lab to pursue a new project investigating sex-based differences in the regulation of neuronal identity.

Also a Professor of Biochemistry and Molecular Biophysics and an Investigator of the Howard Hughes Medical Institute, Dr. Hobert is known for his research using C. elegans to understand the molecular programs that control cell-type differentiation within the nervous system. C. elegans has become an invaluable model organism for studying the nervous system because it contains just over 300 neurons whose development has been studied in great detail.

Recently, electron microscopy was used to compare nervous systems in male and hermaphrodite worms, and showed that some of these neurons are present in both sexes. Interestingly, the researchers discovered that even when these neurons had the same lineage history, position, morphology, and molecular features, there was a striking divergence in the patterns of synapse formation between the sexes. Under the new grant, the Hobert Lab will attempt to identify the mechanisms that control this divergence. The project should produce not only a much deeper understanding of sex-based differences in neuronal identity, but also new resources that will support future investigation of this phenomenon.

Winners of the Javits Neuroscience Investigator Awards are nominated by NINDS staff members and members of the National Advisory Neurological Disorders and Stoke Council (NANDS). The grant acknowledges grant recipients as being leaders in neuroscience who have been highly productive or have contributed paradigm-shifting ideas. By supporting investigators for 4-7 years, the grant also anticipates high productivity in the years to come. 

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Harris Wang Named Office of Naval Research Young Investigator

Gut-Brain Microbiota
A grant from the Office of Naval Research will support the development of three foundational synthetic biology technologies for engineering the human gut microbiota.

Harris Wang, an assistant professor in the Columbia University Department of Systems Biology, has been selected for the Office of Naval Research 2015 Young Investigators Program. This highly selective program promotes the development of early-career academic scientists whose research shows exceptional promise and creativity. With the support of this award, Dr. Wang will extend his research in the field of synthetic biology to develop new technologies for engineering the gut microbiome, the ecosystem of bacteria that inhabit the human digestive system. These new methods, Wang anticipates, could provide new ways of designing communities of different microbial species and ultimately modulating interactions between the gut, the immune system, and the brain.

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Three CUMC Faculty Members Receive Interdisciplinary Appointments

We are pleased to announce that Columbia University Medical Center professors Oliver Hobert, Richard Mann, and Rodney Rothstein have been named to interdisciplinary appointments in the Department of Systems Biology. The addition of this new expertise will expand the breadth of science currently being explored in the Department, enhance educational opportunities for students, facilitate new collaborations, and promote the integration of systems biology perspectives and methods into research being conducted elsewhere in the university.

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Imaging Synapses Using Fluorescent Small Molecule Probes

Imaging synapses

In a test of the Columbia Genome Center's high-content microscopy system, computational image analysis confirmed a high degree of colocalization of green fluorescent protein-labeled synapsin and the dye FM4-64. The researchers plan a high-throughput screen to identify fluroescent small molecules capable of targeting synapses.

Synapses mediate communication between neurons in the brain, making them critical components for neurological activity. Research has shown that synaptic loss and dysfunction play roles in a number of debilitating brain disorders — including Alzheimer’s disease, major depressive disorder, and autism — but currently no effective method exists for identifying and imaging individual synapses in living human brains. Being able to locate and quantify synapses in patients could greatly improve the diagnosis and monitoring of disease, and potentially offer new approaches for treatment.

Clarissa Waites, an assistant professor of pathology and cell biology at the Columbia University College of Physicians & Surgeons, and Dalibor Sames in the Columbia University Department of Chemistry, have recently embarked on a collaboration with the Columbia Genome Center High-Throughput Screening Facility with the goal of identifying small fluorescent molecules that can selectively localize to synapses. If successful, this project could for the first time provide a method for targeting and imaging synapses in the living human brain.

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Genes forming cluster I in the context of cellular signaling pathways

Genes forming cluster I in the context of cellular signaling pathways. Proteins encoded by cluster genes are shown in yellow, and those corresponding to other relevant genes that were present in the input data but not selected by the NETBAG+ algorithm are shown in cyan. 

In a new paper published in the journal Nature Neuroscience, Columbia University researchers report that many of the genes that are mutated in schizophrenia are organized into two main networks. Surprisingly, the study also found that a genetic network that leads to schizophrenia is very similar to a network that has been linked to autism. 

Using a computational approach called NETBAG+, Dennis Vitkup and colleagues performed network-based analyses of rare de novo mutations to map the gene networks that lead to schizophrenia. When they compared one schizophrenia network to an autism network described in a study he published last year, they discovered that different copy number variants in the same genes can lead to either schizophrenia or autism. The overlapping genes are important for processes such as axon guidance, synapse function, and cell migration — processes within the brain that have been shown to play a role in the development of these two diseases. These gene networks are particularly active during prenatal development, suggesting that the foundations for schizophrenia and autism are laid very early in life.

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