News Coverage: Study finds parallels between unresponsive honey bees, autism in humans

Honey bees that consistently fail to respond to obvious social cues share something fundamental with autistic humans, researchers report in a new study. Genes most closely associated with autism spectrum disorders in humans are regulated differently in unresponsive honey bees than in their more responsive nest mates, the study found.

The findings, reported in the Proceedings of the National Academy of Sciences, appear to be unique to genes associated with autism and not to other behavioral disorders in humans. The study offers an early glimpse of the molecular heritage shared across the animal kingdom, the researchers say, and offers tantalizing clues about the evolution of social behavior.

Postdoctoral researcher Michael Saul, left, IGB director and entomology professor Gene Robinson and their colleagues found that genes that are closely associated with autism spectrum disorders in humans are regulated differently in the brains of socially unresponsive honey bees than in bees that behave more typically.
Postdoctoral researcher Michael Saul, left, IGB director and entomology professor Gene Robinson and their colleagues found that genes that are closely associated with autism spectrum disorders in humans are regulated differently in the brains of socially unresponsive honey bees than in bees that behave more typically.

“Some honey bees are more active than others, and some appear indifferent to intruders that threaten the hive. This, in itself, is not unusual,” said University of Illinois entomology professor Gene Robinson, who led the new analysis. “Honey bees take on different roles at different stages of their lifecycle, and not every bee can – or should – function as a guard,” he said.

But when postdoctoral researcher Hagai Shpigler observed that some of those same bees also were unmoved by the presence of a queen larva – a stimulus that typically spurs diligent action in nurse bees – it suggested something unusual was going on, said Robinson, who directs the Carl R. Woese Institute for Genomic Biology at the U. of I.

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News Coverage: Brief interactions spur lasting waves of gene activity in the brain

A five-minute encounter with an outsider spurs a cascade of changes in gene activity in the brain that can last for hours, researchers report in a study of stickleback fish.

The research, described in the journal PLOS Genetics, is one of three recent studies  – the others conducted in honey bees and mice – to see waves of changes in gene expression in the brain 30 minutes to two hours after contact with an intruder.

University of Illinois animal biology professor Alison Bell, graduate student Syed Abbas Bukhari and their colleagues tracked changes in gene expression in the stickleback brain after the fish encountered an intruder.

“We are discovering that social interactions are extremely potent; they provoke big changes in gene expression in the brain,” said University of Illinois animal biology professor Alison Bell, who studies behavior in three-spined stickleback fish. “These very subtle social interactions are getting under the skin and becoming embedded in the brain. Studies like ours are beginning to show how that actually works.” Bell is a member of the IGB’s Gene Networks in Neural & Developmental Plasticity research theme, which supported this research.

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Temporal dynamics of neurogenomic plasticity in response to social interactions in male threespined sticklebacks

Syed Abbas Bukhari, Michael C. Saul, Christopher H. Seward, Huimin Zhang, Miles Bensky, Noelle James, Sihai Dave Zhao, Sriram Chandrasekaran, Lisa Stubbs, Alison M. Bell

Animals exhibit dramatic immediate behavioral plasticity in response to social interactions, and brief social interactions can shape the future social landscape. However, the molecular mechanisms contributing to behavioral plasticity are unclear. Here, we show that the genome dynamically responds to social interactions with multiple waves of transcription associated with distinct molecular functions in the brain of male threespined sticklebacks, a species famous for its behavioral repertoire and evolution. Some biological functions (e.g., hormone activity) peaked soon after a brief territorial challenge and then declined, while others (e.g., immune response) peaked hours afterwards. We identify transcription factors that are predicted to coordinate waves of transcription associated with different components of behavioral plasticity. Next, using H3K27Ac as a marker of chromatin accessibility, we show that a brief territorial intrusion was sufficient to cause rapid and dramatic changes in the epigenome. Finally, we integrate the time course brain gene expression data with a transcriptional regulatory network, and link gene expression to changes in chromatin accessibility. This study reveals rapid and dramatic epigenomic plasticity in response to a brief, highly consequential social interaction.

World of Genomics brings Stubbs lab and IGB research to Chicago

From May 18th to 20th in Chicago, over 15,000 visitors experienced the World of Genomics at the Field Museum of Natural History, a three-day event presented by the Carl R. Woese Institute for Genomic Biology. A large, blue-lit funnel representing the tree of life dominated the space; beneath it, the world’s smallest sequencer read out the genomes of never-before-sequenced organisms currently studied at the IGB.

With six learning stations distributed across Stanley Field Hall, the main floor of the museum where famous T. rex  Sue is displayed, World of Genomics represented the full scope of IGB research in health, technology, and the environment, with hands on activities and exhibits for all ages.

“In all of the outreach events I’ve been a part of, I’ve never experienced such an engaged audience that asked so many excellent, relevant questions about our research,” said Beryl Jones, one of the over 60 volunteers from the IGB who staffed the event. “World of Genomics was truly one of the most rewarding experiences of my PhD, and I feel honored to have been a part of an event that reached so many people.”

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Transcriptional regulatory dynamics drive coordinated metabolic and neural response to social challenge in mice

Michael Saul*, Christopher H Seward*, Joseph M Troy, Huimin Zhang, Laura G Sloofman, Xiaochen Lu, Patricia A Weisner, Derek Caetano-Anolles, Hao Sun, Sihai D Zhao, Sriram Chandrasekaran, Saurabh Sinha and Lisa Stubbs

Agonistic encounters are powerful effectors of future behavior, and the ability to learn from this type of social challenge is an essential adaptive trait. We recently identified a conserved transcriptional program defining the response to social challenge across animal species, highly enriched in transcription factor (TF), energy metabolism, and developmental signaling genes. To understand the trajectory of this program and to uncover the most important regulatory influences controlling this response, we integrated gene expression data with the chromatin landscape in hypothalamus, frontal cortex, and amygdala of socially challenged mice over time. The expression data revealed a complex spatiotemporal patterning of events starting with neural signaling molecules in the frontal cortex and ending in the modulation of developmental factors in the amygdala and hypothalamus, underpinned by a systems-wide shift in expression of energy metabolism-related genes. The transcriptional signals were correlated with significant shifts in chromatin accessibility and a network of challenge-associated TFs. Among these, the conserved metabolic and developmental regulator ESRRA was highlighted for an especially early and important regulatory role. Cell-type deconvolution analysis attributed the differential metabolic and developmental signals in this social context primarily to oligodendrocytes and neurons respectively, and we show that ESRRA is expressed in both cell types. Localizing ESRRA binding sites in cortical chromatin, we show that this nuclear receptor binds both differentially expressed energy-related and neurodevelopmental TF genes. These data link metabolic and neurodevelopmental signaling to social challenge, and identify key regulatory drivers of this process with unprecedented tissue and temporal resolution.

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Behavioral, transcriptomic and epigenetic responses to social challenge in honey bees

H. Y. Shpigler, M. C. Saul, E. E. Murdoch, A. C. Cash-Ahmed, C. H. Seward, L. Sloofman, S. Chandrasekaran, S. Sinha, L. J. Stubbs, G. E. Robinson

Understanding how social experiences are represented in the brain and shape future responses is a major challenge in the study of behavior. We addressed this problem by studying behavioral, transcriptomic and epigenetic responses to intrusion in honey bees. Previous research showed that initial exposure to an intruder provokes an immediate attack; we now show that this also leads to longer-term changes in behavior in the response to a second intruder, with increases in the probability of responding aggressively and the intensity of aggression lasting 2 and 1 h, respectively. Previous research also documented the whole-brain transcriptomic response; we now show that in the mushroom bodies (MBs) there are 2 waves of gene expression, the first highlighted by genes related to cytoskeleton remodeling, and the second highlighted by genes related to hormones, stress response and transcription factors (TFs). Overall, 16 of 37 (43%) of the TFs whose cis-motifs were enriched in the promoters of the differentially expressed genes (DEGs) were also predicted from transcriptional regulatory network analysis to regulate the MB transcriptional response, highlighting the strong role played by a relatively small subset of TFs in the MB’s transcriptomic response to social challenge. Whole brain histone profiling showed few changes in chromatin accessibility in response to social challenge; most DEGs were ‘ready’ to be activated. These results show how biological embedding of a social challenge involves temporally dynamic changes in the neurogenomic state of a prominent region of the insect brain that are likely to influence future behavior.

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Congratulations to Dr Sun.

Congratulations to Dr. Sun for his successful thesis defense entitled: DISSECTING THE REGULATORY ROLES AND CELLULAR FUNCTIONS OF MAMMALIAN ZSCAN5B AND PRIMATE-SPECIFIC PARALOGS!  Calvin is moving on to the Sanford Burnham Prebys Medical Discovery Institute in San Diego, CA.