Wu Tsai Postdoctoral Fellowship in Interdisciplinary Neuroscience and Neuro-related Computer Science

• Fundamental algorithms for visual computation - Visual perception depends on the conversion of light into a neural representation that becomes increasingly complex through sequential stages of processing. Indeed, feature tuning apparently becomes more complex in visual cortex, with a fundamental transition to encoding stimulus orientation. However, recent data from the Demb lab shows fundamental orientation signals much earlier – only a single synapse after the photoreceptors in the mouse retina. Data from the Clark lab shows early orientation signals also in Drosophila. These similar computations in widely divergent phyla suggest a fundamental algorithm for orientation selectivity evolved independently. The postdoctoral fellow will study these newly discovered orientation-tuned interneurons in fly and mouse retina. Experiments will use two-photon imaging, electrophysiology, and genetics to investigate the impact of early-stage orientation tuning on visual computations in neural circuitry and behavior. Comparing algorithms and mechanisms across species will elucidate the requirements and evolution of visual processing. Co-Mentors: Damon Clark (Molecular, Cell, and Developmental Biology); Jonathan Demb (Ophthalmology and Visual Science)

• Parsing predictive processes in cognition - Motor theories of cognition emphasize the role of motor systems in mental processes. Through cognition-action-perception cycles, how we act changes what we perceive and think. The postdoctoral fellow will explore the role of predictive learning and belief formation in cognition-action-perception cycles and whether there are domain-general vs. domain-specific processes in human perception, cognition, and action. Are prediction errors fungible across perception, cognition, and action? Or does each have a unique “neural currency?” Meta-analysis of functional neuroimaging studies favors both possibilities: a domain-general circuit alongside specialized domain-specific prediction errors. The postdoc will build on this foundation, designing studies that reveal the overlap between motor and perceptual learning, with a focus on priors and belief updating, mapping the components of cognition-perception-action cycles and how they interact. We hope to glean fundamental insights that inform our understanding of human social cognition, the engineering of artificial minds, and the blind spots in human reasoning. Co-Mentors: Phillip  Corlett (Psychiatry); Samuel McDougle (Psychology)

• A mechanistic approach to microcircuit-network interaction in human cognition - While studies of non-human animals allow observation of neuronal spiking patterns in individual neurons in relation to behavior, they are limited in assessing features of human-cognition such as subjective awareness of temporal and spatial location, agency, and imaginative experience.  Human recordings from single neurons in subcortical regions that modulate large-scale brain networks (e.g., claustrum) provide an opportunity to link single neuron behavior to brain oscillatory dynamics and cognition. Transient direct electrical brain stimulation of these subcortical regions allows causal manipulations of the circuits that underlie the subjective human experience at a previously inaccessible scale. The co-mentors have developed novel approaches to record and causally manipulate single neurons and large-scale brain networks in humans. The postdoctoral fellow will combine these approaches to examine neuronal population decoding and decipher the neural circuits involved in human higher-order cognition. Co-Mentors: Eyiyemisi Damisah (Neurosurgery and Neuroscience); Laurie Paul (Philosophy and Cognitive Science)
• Understanding Cognitive Aging through Targeted Postmortem Brain Multi-omics - Correlations of genetic variation with cognitive ability have been well studied. However, these analyses do not identify causal genes driving cognitive function across the lifespan. The use of human brain-derived expression datasets could build a foundation on these initial insights and yield genes and molecular pathways altering cognitive function during aging. The postdoctoral fellow will lead a multi-omic study examining the DNA genotyping, methylation, and RNA expression patterns in brain regions associated with confirmed alterations in aging and cognitive decline and compare these patterns across adolescent, adult, and elderly donors. Co-Mentors: Matthew Girgenti (Psychiatry); Hongyu Zhao (Biostatistics)
• From the lab to the real-world: tracking stress effects on learning in adolescence - When can stress help us learn? Stress is an inescapable part of our lives, facilitating our ability to cope with future challenges in part by helping us learn. Stressful events increase during adolescence, a time when the brain is particularly sensitive to stress. The goal of this project is to characterize how stress influences learning during this key period. The postdoctoral fellow will take a multimodal approach to the question of how stress alters learning during development, leveraging clinical and cognitive neuroscience techniques including large-scale neuroimaging data from the ABCD Study as well as smartphone-based ecological momentary assessment to capture real-world stress, learning, and memories. This multimodal approach will provide the basis for a comprehensive framework for the conditions under which stress promotes learning in adolescence, with key implications for understanding resilience and adaptive cognition. Co-Mentors: Elizabeth Goldfarb (Psychiatry); Dylan Gee (Psychology)
• A deep look: adaptive optics-enhanced multiphoton imaging of subcellular neuronal activity - Compared to calcium indicators, genetically encoded voltage sensors provide direct and more immediate measures of a cell’s electrical activity, yet they exhibit lower brightness and signal-to-noise, a major challenge to their use in the brain.  The application of adaptive optics (AO) methods would correct aberrations in the light path induced by imaging components and tissue heterogeneity. The postdoctoral fellow will develop novel AO tools in combination with fast, random-access scanning to yield high-fidelity measurements of neuronal membrane potential in subcellular compartments (e.g., dendritic spines) of the awake, behaving mouse. This project will produce novel microscopy tools and fundamental insights into dendritic signaling. Co-Mentors: Michael Higley (Neuroscience); Cristina Rodríguez (Biomedical Engineering)
• Multimodal manifold learning and analysis of emotion and facial states in dyadic interactions - This project aims to understand how facial expressions communicate emotion between human partners. It is proposed that facial mimicry and overlapping neural circuits between social and motor functions underlie this fundamental interactive behavior. The postdoctoral fellow will apply hyperscanning neuroimaging techniques—using optical methods and functional near infrared spectroscopy (fNIRS)—to isolate the neural underpinnings of face processes related to emotional expressions.  Machine and manifold learning will be used to determine the features of the interaction that are specific to the transfer of emotion across partners. The fusion of these two disciplines will create novel tools to investigate dyadic human social cognition, advance understanding of a fundamental social behavior, and provide insights about social behavior disorders. Co-Mentors: Joy Hirsch (Psychiatry); Smita Krishnaswamy (Genetics and Computer Science) 
• Action in the cognitive map: Motor representations in hippocampal memory - Memories for actions versus individual episodes are often linked to distinct memory systems. However, action can be a critical dimension of episodic memory.  The postdoctoral fellow will lead a novel research program examining the cooperation between motor and episodic memory systems. This project will require developing a novel framework of movement-related representational principles in brain areas not traditionally linked to movement. It will call upon cutting-edge behavioral and computational methods, as well as multivariate fMRI and MEG techniques typically used to characterize neural representations of objects, contexts, and visual scenes, extending them to the representation of actions. Co-Mentors: Samuel McDougle (Psychology); Elizabeth Goldfarb (Psychiatry)
• Trans-species neurobehavioral assays of tactile sensory perception - The postdoctoral fellow will apply parallel tactile sensory paradigms combined with video-EEG recordings to assess cortical activity in mice and humans. Though the value of trans-species biomarkers is well recognized, there are currently no validated batteries to quantify sensory function in this regard.  Considering that the circuitry for sensory processing is well-characterized and conserved across species, the animal model will provide a gateway to address mechanistic questions that will be further validated in humans. The project will benefit from expertise from the McPartland lab, which studies electrophysiological brain responses to sensory percepts in humans, and the Bordey lab, which uses mice to study the neurodevelopmental mechanisms leading to sensory deficits in tuberous sclerosis complex. Co-Mentors: James McPartland (Psychology); Angelique Bordey (Neurosurgery)
• Network analysis of the primate prefrontal-limbic mechanisms underlying cognitive and motivational regulation - This project seeks to understand how complex spatiotemporal features of network activity mediate diverse elements of cognition and motivation. The postdoctoral fellow will perform high-density, large-scale neural recordings guided by high-precision neuronavigation, in rhesus macaques participating in a behavioral game in which cognitive demands and the parameters of gains/losses can be independently and quantitatively manipulated. Chemo- and opto-genetic tools will allow specific manipulation of circuits and neuronal populations. By linking neuronal-, circuit-, and network-level analyses and genetic and computational tools, the postdoctoral fellow will advance understanding of the fundamental mechanisms underlying human intelligence. Specifically they will be able to explore how the collective and interactive dynamics of constituent nodes across dorsal and ventral aspects of prefrontal-limbic networks produce dynamic and stable neural memories critical for cognitive and motivational functions; how changes in the input/output functions of individual nodes propagate and contribute to the transition of network states; and how the global state of the network affects the response of individual nodes.  Co-Mentors: Hyojung Seo (Psychiatry); In-Jung Kim (Ophthalmology)
• A novel neuronal metabolic biochemical pathway affecting cognition - Cellular metabolism is critical for neurological function. Yet, many metabolic biochemical principles that balance the chemicals in the brain remain unknown. Characterizing disease-associated metabolic genes of unknown function may advance our fundamental understanding of metabolic biochemistry in the central nervous system (CNS). SLCO1A2 is an uncharacterized CNS transporter associated with Progressive Supranuclear Palsy (PSP), a late-onset degenerative tauopathy with symptoms that include loss of balance and cognitive impairment. While genomic data suggests that SLCO1A2 loss-of-function mutations increase disease risk, the transporter’s physiological ligand and in vivo function are unknown. The postdoctoral fellow will explore SLCO1A’s impact on metabolomics in iPSC-derived brain cells and employ intravital imaging in mouse models to understand the gene’s in vivo function in neurons and glia. Ultimately, understanding SLCO1A2’s role in health and disease may shed light on the links between neuronal metabolism and cognitive function. Co-Mentors: Hongying Shen (Cellular and Molecular Physiology); Jaime Grutzendler (Neurology and Neuroscience)

• Microbiome modulation of nervous system developmental plasticity - How the microbiome affects neural development is only beginning to be appreciated and is mechanistically largely unknown. We recently found that the nutritional state of C. elegans affects sensory neurite remodeling, and identified a conserved pathway required for remodeling only in bacteria-fed animals. This remodeling also requires the activity of a well-known metabolic sensor, TORC2, suggesting that commensal microbes modulate nervous system development and function and providing an experimental handle to explore this modulation. The postdoctoral fellow will examine how gut microbial metabolites impact dendrite remodeling, identify host mechanisms mediating these effects, and elucidate behavioral impacts – possibly revealing how symbiotic microbes evolve to regulate nervous system function.  The project will employ bacterial genetics and metabolomics analysis, unbiased genetic approaches, and quantitative analysis of calcium imaging and sensory-driven behavior. Co-Mentors: Shaul Yogev (Neuroscience and Cell Biology); Mike O'Donnell (Molecular, Cell, and Developmental Biology)

Award and Expectations

Selected Fellows will receive:

• Postdoctoral Associate appointment at Yale.  Generous stipend (well beyond NIH starting levels), with a cost-of-living increase for a maximum of three years. Salaries vary by track.
• Funds for professional development and relocation support
• Professional development and community-building activities
• Access to cutting-edge space, equipment, facilities, and services in the upcoming new home of WTI at 100 College Street in New Haven, CT

WTI Postdoctoral Fellows are expected to:

• Begin their appointment on or before September 1^st, 2023, if possible
• Agree to the WTI code of conduct
• Participate in WTI activities and devote effort toward professional development, service, and community-building (up to 10% of effort)
• Submit an annual progress report
• Follow all Yale guidelines and requirements for postdocs

Instructions for Submissions

The application period for the Postdoctoral Fellowships Program closes December 15, 2022.

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The same submission and selection process apply to both the Data and Computer Science Track and Experimentalist Track.

Eligibility and Selection

• PhD degree or equivalent awarded by the beginning of the Fellowship or within the last 3 years
• The fellowship is open to non-U.S. citizens
• A track record of cross-cutting scientific discoveries and community building
• Because this fellowship is meant to build the number of researchers working in these areas at Yale, current members of the Yale community (including postdocs and PhD students) are not eligible to apply
• Particularly interested in scientists with a genuine commitment to diversity, equity, and inclusion (DEI) in science and who represent a diversity of backgrounds, perspectives, and identities, including those from backgrounds historically underrepresented in the sciences, as defined by the NIH
• Fellows are selected by a committee of faculty and Institute leaders and are chosen based on their interdisciplinary scientific goals and achievements, commitment to advancing DEI, and ability to make meaningful contributions to the community

Submission Process

All applications must include:

• Cover letter - Please identify the priority research area to which you are applying (see above). Describe your interest in the interdisciplinary mission of the WTI and why you are interested in joining our community and becoming part of this program (page 1).
• Research statement - Summarize prior research experiences and contributions and describe your postdoctoral research interests. We are particularly interested in how you envision advancing understanding of human cognition.
• DEI statement - Please describe how your unique background, identity or experience will contribute to diversity, equity, or inclusion at WTI, Yale, and in science (2 pages).
• Two letters of recommendation - One letter must be from your thesis advisor(s). The letters should address the quality, originality, and independence of your research and potential. Letters must be received by the submission deadline. Incomplete applications will not be reviewed.
• Curriculum vitae - Please provide a current CV, including papers that are published, in press, or deposited in preprint server (e.g., bioRxiv or arXiv).

Timeline

December 15, 2022 – Deadline for WTI Postdoctoral Applications

Mid-March 2023 – Recipients of Wu Tsai Postdoctoral Fellowships announced

Contact

Please contact wti@yale.edu for any questions related to this application