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Daniel Weatherill
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Neuroscientist/Data Scientist | Advancing ALS Research Through AI & Multimodal Data Integration
Los Angeles, California, United States
Résumé
Jobs
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Data ScientistTarget ALSMay 2025 - Current (1 year 2 months)Understanding neurodegenerative diseases like ALS requires the integration of diverse, high-dimensional datasets. In this role, to support the development of scalable data infrastructure and tools to accelerate discovery and therapeutic advancement, I: • Analyze multi-omics datasets (genomic, transcriptomic, proteomic) related to brain function and neurodegenerative disease • Build and manage data pipelines and databases to support large-scale experimental and clinical research • Curate and integrate high-quality datasets into the Target ALS Data Engine to fuel hypothesis generation and validation • Collaborate cross-functionally to translate complex findings into clear, actionable insights for both scientific and non-scientific stakeholder- Associate Project ScientistUCLASep 2022 - May 2025 (2 years 9 months)Cancer cells must tightly regulate energy production and redox potential to support their high metabolic demands. Disruption of this balance can induce cell death, providing a potential therapeutic window. To further explore this treatment strategy, in this role, I: • Employed data-driven modeling to characterize metabolic network states linked to cancer cell survival and death in well-established cell lines treated with FDA-approved chemotherapeutics • Analyzed multi-omics profiles using in silico genome-scale models to identify candidate metabolic targets for intervention • Contributed to the development of a pipeline for generating 3D patient-derived cultures, with the aim of mapping their omics data onto genome-wide metabolic networks f
- Lead ResearcherUCLAMay 2021 - May 2025 (4 years 1 month)Traditional behavioral measures in fear research often rely on binary readouts like freezing versus non-freezing, limiting our ability to study fear as a graded, continuous mental state. To address this, in this role, I: • Led the development and implementation of a pipeline that applies deep learning-based keypoint tracking to video of rodents performing an avoidance learning task • Employed supervised and unsupervised machine learning approaches to identify and characterize behavioral postures correlated with task performance • Developed a novel framework for quantifying fear as a continuous behavioral state, advancing alignment between behavioral analysis and modern theoretical models of emotion • Helped establish a new methodological st
- Assistant ResearcherUCLASep 2014 - Jun 2022 (7 years 10 months)Despite major advances in identifying neurons activated during memory recall, pinpointing the actual sites of memory storage in the mammalian brain remains a fundamental challenge. To continue to address this, in this role, I: • Designed a method to label and visualize, within a defined time window, only those synaptic connections undergoing plasticity believed to underlie memory formation • Validated this method in cultured neurons as a precursor to in vivo application in rodent models • Developed an experimental framework to compare memory trace architecture following weak versus strong learning, aiming to reveal how memory strength influences storage mechanisms • Contributed to bridging a long-standing gap in memory research by targeting
- Postdoctoral FellowNational Centre for Biological Sciences NCBSAug 2012 - Aug 2014 (2 years 1 month)Despite major advances in identifying neurons activated during memory recall, pinpointing the actual sites of memory storage in the mammalian brain remains a fundamental challenge. To begin to address this challenge, in this role, I: • Coordinated the construction of a biosafety level 2 research facility • Designed, built, and calibrated an optical system for optogenetic stimulation • Performed optogenetic electrophysiology experiments to support behavioral experiments in a high-profile paper characterizing memory allocation
- Postdoctoral FellowUniversité de MontréalSep 2010 - Jun 2012 (1 year 10 months)Excess excitatory signaling in the brain—often driven by dysregulated protein synthesis—has been implicated in autism spectrum disorders (ASDs). In this role, to contribute to research illuminating the role of mTOR, a key regulator of translation, and its downstream effectors in ASD-related pathology, I: • Investigated signaling pathways downstream of mammalian target of rapamycin (mTOR) involved in translational control relevant to ASD phenotypes • Contributed to defining a translational regulation cascade linking mTOR activity to ASD-like behavioral and synaptic alterations in rodent models
Education
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- Doctor of Philosophy (Ph.D, NeuroscienceMcGill UniversityJan 2003 - Dec 2010 (8 years)Target of rapamycin (TOR) complex 1 (TORC1), a key regulator of translation, has been implicated in numerous forms of long-term synaptic plasticity and memory. A powerful model system for studying the changes underlying memory formation is synaptic facilitation at sensory-to-motor neuron synapses in the sea slug, Aplysia, as both short- and long-term forms of this type of synaptic plasticity have been shown to contribute to short- and long-term memory, respectively, for behavioural sensitization of the gill-/siphon-withdrawal reflex. For my PhD studies, I characterized the nature of the signalling pathways through which TORC1 regulates translation during long-term facilitation (LTF) at sensory-to-motor neuron synapses.
- Bachelor’s Degree with Honors, BiologyMcGill UniversityJan 2000 - Dec 2003 (4 years)
Projects (professional or personal)
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Awards
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- WEarly Career FellowshipWellcome TrustDBT India AllianceAug 2012
- LPostdoctoral Training AwardLe Groupe de Recherche sur le Système Nerveux Central Universite de MontrealSep 2010
- FDoctoral Training AwardFonds de Recherche en Santé du QuébecJan 2006
- MJeanne Timmins Costello ScholarshipMontreal Neurological Institute McGill UniversitySep 2003
- NUndergraduate Student Research AwardNatural Sciences and Engineering Research Council of CanadaMay 2001
- Scholar’s Advantage ScholarshipUniversity of CalgarySep 1998
- SAlexander Rutherford ScholarshipStudent Aid AlbertaSep 1998
Publications
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- NIsolation of the differential effects of chronic and acute stress in a manner that is not confounded by stress severityNeurobiology of StressFeb 2024Firm conclusions regarding the differential effects of the maladaptive consequences of acute versus chronic stress on the etiology and symptomatology of stress disorders await a model that isolates chronicity as a variable for studying the differential effects of acute versus chronic stress. This is because most previous studies have confounded chronicity with the total amount of stress. Here, we have modified the stress-enhanced fear learning (SEFL) protocol, which models some aspects of posttraumatic stress disorder (PTSD) following an acute stressor, to create a chronic variant that does not have this confound. Comparing results from this new protocol to the acute protocol, we found that chronic stress further potentiates enhanced fear-l
- ESynapse formation changes the rules for desensitization of PKC translocation in AplysiaEuropean Journal of NeuroscienceFeb 2015Protein kinase Cs (PKCs) are activated by translocating from the cytoplasm to the membrane. We have previously shown that serotonin-mediated translocation of PKC to the plasma membrane in Aplysia sensory neurons was subject to desensitization, a decrease in the ability of serotonin to induce translocation after previous application of serotonin. In Aplysia, changes in the strength of the sensory–motor neuron synapse are important for behavioral sensitization and PKC regulates a number of important aspects of this form of synaptic plasticity. We have previously suggested that the desensitization of PKC translocation in Aplysia sensory neurons may partially explain the differences between spaced and massed training, as spaced applications of
- HExploring Mechanisms of Synaptic Plasticity Using Exogenous Expression of Proteins at the Sensory-to-Motor Neuron SynaHumana PressJan 2013The use of expression constructs to drive exogenous expression of proteins has long been a pillar of cell and molecular biology. In this chapter, we will focus on two particular uses for this technique in studying synaptic plasticity, using Aplysia californica as a model: first, the use of overexpressed fluorescent proteins as reporters for live imaging of signal transduction pathways that are activated during synaptic plasticity, and, second, exogenous expression of dominant negatives to test the role of specific signaling pathways in synaptic plasticity. The advantages and disadvantages of these techniques will be discussed followed by detailed experimental methods describing how to use these techniques.
- NAutism-related deficits via dysregulated eIF4E-dependent translational controlNatureJan 2013Hyperconnectivity of neuronal circuits due to increased synaptic protein synthesis is thought to cause autism spectrum disorders (ASDs). The mammalian target of rapamycin (mTOR) is strongly implicated in ASDs by means of upstream signalling; however, downstream regulatory mechanisms are ill-defined. Here we show that knockout of the eukaryotic translation initiation factor 4E-binding protein 2 (4E-BP2)—an eIF4E repressor downstream of mTOR—or eIF4E overexpression leads to increased translation of neuroligins, which are postsynaptic proteins that are causally linked to ASDs. Mice that have the gene encoding 4E-BP2 (Eif4ebp2) knocked out exhibit an increased ratio of excitatory to inhibitory synaptic inputs and autistic-like behaviours (that
- JCompartment-specific, differential regulation of eukaryotic elongation factor 2 and its kinase within Aplysia sensory neJournal of NeurochemistryJun 2011Long-term facilitation (LTF) in Aplysia is a leading model for elucidating the biochemical mechanisms of synaptic plasticity underlying learning. LTF requires translational control downstream of target of rapamycin complex 1. Our lab has previously shown that treatment with the facilitating neurotransmitter, 5-hydroxytryptamine (5-HT), causes a target of rapamycin complex 1-mediated decrease in phosphorylation of eukaryotic elongation factor 2 (eEF2) within the neurites of sensory neurons involved in LTF. Here, we characterize the Aplysia orthologue of eEF2 kinase (eEF2K). We show that the Aplysia eEF2K orthologue contains an S6 kinase phosphorylation site and that a serine-to-alanine mutation at this site blocks the ability of 5-HT to decr
- JRibosomal protein S6 kinase is a critical downstream effector of the target of rapamycin complex 1 for long-term facilitJournal Of Biological ChemistryFeb 2010Long-term facilitation (LTF) in Aplysia is a leading cellular model for elucidating the biochemical mechanisms of synaptic plasticity underlying learning. In Aplysia, LTF requires translational control downstream of the target of rapamycin (TOR) complex 1 (TORC1). The major known downstream targets of TORC1 are 4E binding protein (4E-BP) and S6 kinase (S6K). By removing the site within these regulators required for their interaction with TORC1, we have generated dominant negative proteins that disrupt specific pathways downstream of TORC1. Expression of dominant negative S6K, but not dominant negative 4E-BP, in Aplysia sensory neurons (SNs) blocked 24-h LTF. TORC1 is directly activated by the small GTP-binding protein, Ras homologue enriche
- JPKC Differentially Translocates during Spaced and Massed Training in AplysiaJournal of NeuroscienceAug 2009Learning is highly regulated by the pattern of training. In Aplysia, an important organism for the development of cellular and molecular models of learning, spaced versus massed application of the same stimulus leads to different forms of memory. A critical molecular step underlying memory is the serotonin (5HT)-mediated activation of the novel PKC Apl II. Here, we demonstrate that activation of PKC Apl II is highly sensitive to the pattern of 5HT application. Spaced applications downregulate PKC translocation through PKA signaling, whereas massed applications lead to persistent translocation of PKC. Differential regulation of PKC translocation is mediated by competing feedback mechanisms that act through protein synthesis. These studies el
- MPhysiological Role for Phosphatidic Acid in the Translocation of the Novel Protein Kinase C Apl II in Aplysia Neurons▿Molecular and Cellular BiologyAug 2008In Aplysia californica, the serotonin-mediated translocation of protein kinase C (PKC) Apl II to neuronal membranes is important for synaptic plasticity. The orthologue of PKC Apl II, PKCε, has been reported to require phosphatidic acid (PA) in conjunction with diacylglycerol (DAG) for translocation. We find that PKC Apl II can be synergistically translocated to membranes by the combination of DAG and PA. We identify a mutation in the C1b domain (arginine 273 to histidine; PKC Apl II-R273H) that removes the effects of exogenous PA. In Aplysia neurons, the inhibition of endogenous PA production by 1-butanol inhibited the physiological translocation of PKC Apl II by serotonin in the cell body and at the synapse but not the translocation of PK
- JModulation of heart activity during withdrawal reflexes in the snail Helix aspersaJournal of Comparative Physiology AApr 2005The beating activity of the molluscan heart is myogenic, but it is influenced by nervous signals of central origin. Previous studies have demonstrated changes in cardiac output during feeding and other behaviors. Here, we describe a short latency, transient cardiac response that accompanies withdrawal reflexes. When evoked by electrical stimulation of peripheral nerves, the response was detected within one or two heartbeats. Beat amplitudes increased on average 11.6%, and inter-beat intervals decreased on average 2.1%. The mean duration of the response was 28.1 s. A transient inhibitory phase often preceded the excitatory response. Results from testing various nerves and tissues show that the cardiac responses invariably occur whenever cont
- AWhy the ovotestis of Helix aspersa is innervatedActa Biologica HungaricaMay 2004Although Schmalz described the innervation of the ovotestis in pulmonate snails as early as 1914, no functions have been attributed to it. In H. aspersa, the intestinal nerve branches profusely within the ovotestis and terminates in the walls of the acini and in the sheath surrounding the early portion of the hermaphroditic duct. We found both sensory and motor functions for this innervation. Significantly, there is a tonic sensory discharge generated by the mechanical pressure of growing oocytes, and the level of tonic afferent activity is strongly correlated with the number of ripe oocytes; this is probably a permissive signal that gates ovulation. Tactile stimulation of the ovotestis causes a phasic sensory discharge and a pronounced car