eLife and COVID-19: Keeping communications open with online research talks

AANAT1 functions in astrocytes to regulate sleep homeostasis presented by Sejal Davla, Advanced Science Research Center, United States

Sejal describes their talk:
“Astrocytes in the fruit fly brain use an enzyme AANAT1 that catabolizes monoamines such as dopamine and serotonin to control the amount of recovery sleep after prolonged sleep deprivation.”

RNA isoform screens reveal the essentiality and tumor suppressor activity of ultraconserved poison exons presented by James Thomas, Fred Hutchinson Cancer Research Center, United States

James describes their talk:
“RNA alternative splicing is essential for normal tissue development and homeostasis but, when misregulated, drives pathogenesis in dozens of human disorders. While RNA-seq provides a means to comprehensively catalog the expression of individual RNA isoforms, no correspondingly high-throughput methodology exists to functionally interrogate each of these. To address this, we developed pgFARM (paired guide RNAs for alternative exon removal) - a CRISPR/Cas9-based method to manipulate alternative splicing independent of gene inactivation.”

Probe-Seq enables transcriptional profiling of specific cell types from heterogeneous tissue by RNA-based isolation presented by Ryoji Amamoto, Harvard Medical School

Ryoji describes their talk:
“Probe-Seq is a novel method that allows for RNA sequencing of potentially any cell type from potentially any organism. It leverages FISH labeling of RNA markers that are specific to certain cell types to FACS isolate and downstream transcriptional profiling. We showed that it can be used in human, mouse, chick, and Drosophila cells, suggesting that it may be of interest to a broad audience.”

Striatal function and its role in goal directed action: a (learning) update presented by Dr Miriam Matamales, University of New South Wales

Miriam describes their talk:
"One of the most intriguing characteristics of the striatum is the random spatial distribution and high degree of intermingling between its D1-(direct) and D2-(indirect) spiny projection neurons (SPNs). The anatomical organisation of these two principal neuronal populations is actively promoted during development and has been highly conserved throughout evolution for over 500 million years, and yet its relationship to function is still not fully understood. In our recent study, by mapping a dopamine-dependent transcriptional activation marker in large ensembles of D1- or D2-SPNs in mice, we demonstrated an extensive and dynamic D2- to D1-SPN transmodulation across the striatum that is necessary for updating previous goal-directed learning."

Perception and encoding of temporally fluctuating odour stimulus in mice presented by Debanjan Dasgupta, The Francis Crick Institute, United Kingdom

Debanjan describes their talk:
"The field of olfaction has largely been dominated by the notion of being a temporally slow sense and hence temporal structure in odour had not been accounted for a long time. Here, we show that mice can understand correlation in temporal patterns in odour stimulus at frequencies > 40Hz. Further, we observe neurons in the olfactory bulb that can follow frequency upto 20 Hz suggesting the presence of vital neuronal machinery to use naturally occurring temporal patterns in odour stimulus."

Interneurons intelligent operations: It's a matter of nonlinear dendrites presented by Alexandra Tzilivaki, Charité – Universitätsmedizin Berlin, Germany

Alexandra will present “Our recent modelling predictions, where we challenge the hypothesis that interneurons act simply as linear, widespread inhibitory, blankets across neuronal circuits. Along with supporting experimental evidence that I would briefly highlight, we demonstrate that a major interneuron subtype in CA3 and mPFC - the Fast Spiking Basket cells- contain two types of nonlinear dendrites that support learning and memory functions and are better described by a nonlinear Artificial Neural Network similar to pyramidal neurons. The below proposition raises questions for further studies in order to understand whether interneurons are assistants of leaders in memory formation.”

Internal state configures olfactory behavior and early sensory processing in Drosophila larva presented by Katrin Vogt, Harvard University, United States

Katrin describes their talk:
“We discovered that an early olfactory processing center, the antennal lobe, is a bona fide decision making circuit for innate olfactory behavior. Well-fed animals are repelled by certain odors, however food-deprived animals are attracted to the same odors. Combining connectomics, behavioral experiments and functional imaging in genetically modified animals, and computational modeling, we have discovered how this state-dependent decision to assign positive or negative valence to an odor is computed by serotonergic modulation in the antennal lobe.”

Ventral pallidal neurons modulate accumbal activity to amplify reward value presented by Meaghan Creed, Washington University, St. Louis, United States

Meaghan describes their talk:
“Decades of research has shown (and we confirm) that inhibition of the nucleus accumbens is necessary for reward consumption; however the neural substrate of this inhibitor is not understood. Ventral pallidum neurons encode reward value, but the VP is considered an output on the NAc in classic models of the basal ganglia. Challenging this classical model, we show that non-canonical VP neurons signal reward value to the NAc by potently inhibiting their activity to promote reward consumption on fast time scales.”

Hippocampal and Prefrontal Theta-Band Mechanisms Underpin Implicit Spatial Context Learning presented by Eelke Spaak, Donders Institute, Radboud University, Netherlands

Eelke describes their talk:
“Humans are very good at learning where to expect certain items, given their spatial context; but how is this contextual structure learned, and how is this knowledge exploited? Using magneto-encephalography (MEG) and computational modelling of search behaviour, we show that learning is transient and depends on the hippocampal theta rhythm, whereas exploitation is sustained and depends on theta activity in the prefrontal cortex. Interestingly, the amount of explicit knowledge observers were able to form about spatial regularities in the task was *inversely* related to the behavioural benefit, thus demonstrating that this effect is implicit in nature.”

Stemness regulation by an oncogenic PIK3CA activity threshold presented by Ralitsa Madsen, University College London, United Kingdom

Ralitsa describes their talk as:
"A systems biology approach demonstrates that high oncogenic PI3K pathway activation is strongly linked to stabilisation of a stemness transcriptional network in human pluripotent stem cells (hPSCs). Using an allelic series of CRISPR-engineered hPSCs, we demonstrate a near-binary phenotypic ‘switch' in homozygous PIK3CA-H1047R hPSCs - which ultimately becomes refractory to targeted PI3K inhibition. The stabilised stemness state is instead maintained by self-sustained TGFbeta/NODAL pathway activation. This mechanism has implications for understanding the dose-dependent effects of oncogenic PIK3CA in the context of human cancer."

An evolutionarily conserved truncated PD-L1 variant functions as a soluble receptor antagonist presented by Kevin Ng, The Francis Crick Institute, United Kingdom

Kevin describes their talk:
“The PD-1-PD-L1 axis restrains immune responses and is a major therapeutic target across a variety of cancer types. In our recent eLife paper, we described a truncated PD-L1 variant that functions as a receptor antagonist and attenuates the immunosuppressive capacity of transmembrane PD-L1. I will describe our follow-up work on this molecule, focusing on the function of soluble PD-L1 in cancer and autoimmune disease.”

Synteny-based analyses indicate that sequence divergence is not the main source of orphan genes presented by Dr. Nikolaos Vakirlis, Alexander Fleming Biomedical Sciences Research Center, Greece

Nikolaos describes their talk:
“Homology information implicit in regions of conserved synteny allows to quantify gene origination by complete sequence divergence, revealing a larger-than-expected role for other mechanisms of origin, including de novo origination”

Expandable and reversible copy number amplifications drive rapid adaptation to antifungal drugs presented by Robert Todd, Creighton University, United States

Robert describes their talk:
"In the primary human fungal pathogen, Candida albicans, copy number variations (CNVs) amplify genes that are both necessary and sufficient to confer antifungal drug resistance. Here, we describe the rapid and recurrent acquisition of novel, complex CNVs during adaptation to azole antifungal drugs. These findings support a novel mechanism for the rapid acquisition of antifungal drug resistance and provide new genomic evidence for the phenotypic heterogeneity and antifungal drug tolerance frequently observed in clinical settings."

Generating multi-scale predictive networks of Northern Corn Leaf Blight resistance presented by Natalie Clark, Iowa State University, United States

Natalie describes their talk:
"Northern Corn Leaf Blight (NLB) is one of the most significant corn diseases, causing the largest crop loss of any disease in the Northern United States from 2012-2015. Understanding how gene expression correlates with specific disease phenotypes is critical for developing disease-resistant crops that enhance global food security and limit economic losses. In my talk, I will describe how we have integrated transcriptome and proteome measurements with disease phenotyping and computational modeling to build predictive regulatory networks of NLB resistance."

SARS-CoV-2 infected host cell proteomics reveal potential therapy targets presented by Dr. Christian Münch, Goethe University, Frankfurt

Christian describes their talk:
"I will present a human cell line model for SARS-CoV-2 infection in which we characterized the host cell proteome and translatome response. We uncovered a number of host pathways modified by the virus. Using drugs inhibiting these pathways, we found that these efficiently block SARS-CoV-2 replication."

You can read about Christian's research (which is currently published as a preprint) here.

Neuroscience of volition for decisions that matter presented by Uri Maoz, Chapman University, United States

Uri describes their talk:
"Well-known results in neuroscience suggest that consciousness may not be part of the causal chain leading to action in humans, providing evidence against free will. However, those results focus on arbitrary, meaningless decisions (e.g., raising your left/right hand for no reason or purpose) while the free-will debate focuses on deliberate decisions (e.g., selecting a charity to donate). We show that there might be different neural mechanisms for deliberate and arbitrary decisions, and thus that these famous results may not generalize from arbitrary to deliberate decisions challenging their applicability to the free-will debate."

Categorical representation from sound and sight in the ventral occipito-temporal cortex of sighted and blind presented by Stefania Mattioni, UCLouvain, Belgium

Stefania describes their talk:
"The world is full of rich and dynamic visual information. To avoid information overload, the human brain groups inputs into categories such as faces, houses, or tools. A part of the brain called the ventral occipito-temporal cortex (VOTC) helps categorize visual information. However, it is not clear how the VOTC characterizes information. In our study we investigate the nature of categorical representation and functional organization of VOTC presenting different categories in visual and auditory format, in sighted and in early blind individuals."

Role of RhoJ in fibronectin fibrillogenesis during angiogenesis presented by Ananthalakshmy Sundararaman, University of Bristol, United Kingdom

Ananthalakshmy describes their talk:
"Angiogenesis requires endothelial cells to remodel the extracellular matrix. RhoJ regulates active integrin trafficking to negatively regulate fibrillogenesis. RhoJ competes with its ancestral protein Cdc42 for shared effectors to regulate fibronectin fibrillogenesis in opposing directions."

Multiscale analysis of liver tissue organization presented by Hernán Andrés Morales-Navarrete, Pontificia Universidad Católica del Ecuador

Hernán decribes their talk:
"We studied the structural organization of liver tissue by combining confocal microscopy, digital image reconstruction and soft-condensed-matter-physics concepts. Liver tissue follows of a hierarchical multiscale order that emerges from local cellular self-organization."

Probing Myelin in First Episode of Psychosis with MRI: A Framework to Understand Negative Symptoms and Verbal Memory presented by Carolina Makowski, University of California San Diego, United States

Carolina describes their talk:
"When one speaks of psychotic disorders, positive symptoms (e.g. hallucinations, delusions) often come to mind; however, negative symptoms (e.g. amotivation, flattened affect) and verbal memory deficits are also core features of these disorders with no known treatments. My talk will focus on neuroanatomical features measured with MRI, with an emphasis on putative myelin markers, which may underlie negative symptoms and verbal memory deficits after a first episode of psychosis. I will show evidence that hippocampal connectivity may play a large role in shaping these symptom constructs, and propose that treatments targeting the hippocampus may have an impact on clinical outcomes in psychosis."

The proteome landscape of pediatric leukemia in patients and xenograft models presented by Dr. Philipp Lange, University of British Columbia, Canada

Philipp describes their talk:
"Patient derived xenograft models are a powerful tool to interrogate cancer biology, however it is not well understood what aspects of the proteome are accurately recapitulated by the model. Based on integration of the genomic, proteomic and PTM data we show that the proteome landscape of primary pediatric acute leukemias is largely recapitulated in murine patient derived xenografts. We also present data showing that select pathways differ between primary and xenograft cells and that the host environment has greater impact on post translational modifications than protein abundance."