NanoCourses

NanoMaster: Joseph Dougherty | dougherty@wustl.edu

Synopsis

The goal of this 7-session (90 min each) fellowship-writing workshop is to develop and submit an F30/F31 grant for the December 8 deadline.

Pre-requisite

Students must have finished the first year spring grant-writing courses, and be in a thesis lab. They should have one or more ‘rough ideas’ for a grant topic, with the intention to submit the grant Dec 8th – hence we assume this will be of interest primarily to 2nd and 3rd year students. If you are interested in submitting at a different time in the grant cycle, other workshops exist that would be a better fit.

Learning objectives

The goal of this nano-course is to learn efficient ways to write an NIH F30/F31 fellowship. At the end of the course student should know:

• How to identify a research topic that is suitable for an NIH grant.
• How NIH grants are scored and how reviewers think as they evaluate grants.
• Which documents are prepared for an NIH grant.
• How each document contributes to that score.
• How to prepare a clear and effective NIH grant.

Students will achieve these objectives by going through the process of writing an NIH grant for the F30/F31 Dec 08 deadline. The course will be a mixture of lectures on grant writing, intermixed with writing workshops and opportunities for feedback from peers and faculty. Research sections will be done first so there is time to identify additional preliminary data as needed.

Assignments/evaluation

This is a course and homework will be treated as such. Students will be graded on turning in drafts of the required sections of the grant on time (Monday preceding each class – 90%) and their active participation in a mock study section (10%).

September 6 | Introduction

• Lecture: Overview of how NIH grants are scored (15 min); Overview of syllabus (10 min); Development of a Specific Aims page (15 min)
• Exercise: brainstorming aims (45 min); selecting recommendation letter writers
• Assignment (due Monday at noon, prior to next session): Draft of Specific Aims page (1 page)

September 20 | Specific Aims & Research Strategy sections

• Exercise: Small groups (4-5 students + 1 faculty) review Specific Aims, 10 min/person(40-60 min)
• Lecture: Research Strategy section (20-30 min)
• Assignment (due Monday at noon, prior to next session): Revised Specific Aims page (1 page) and draft Research Strategy Section (5 pages, including mock figures, but not counting references)

October 4 | Specific Aims & Research Strategy sections

• Exercise: Small group review of Research Strategy section (15 min per person, 60 min total).
• Lecture: How to use Zotero (10 min)
• Exercise: Define wish list of training activities from grant
• Assignment (due Monday at noon, prior to next session): Revised Aims + Revised Research Strategy (now with better figures (part of the 5 pages), and referenced) + Bulleted list of 4-6 goals for training and 1-2 concrete activities that help meet each goal

October 18 | Bring your mentor to work day

• Lecture: F2 Background; Goals for Training; F6 Selection of Sponsor; F9 Sponsor and Co-Sponsor statements your mentor needs to write it, but with a lot of your input
• Exercise: Background & Goal Brainstorming, Training plan revision, draft outline of F2/F9 with mentor
• Flipped lecture: How do study sections work? (get video of a mock study section from ICTS)
• Materials: Instructions for peer review
• Assignment (due Monday at noon, prior to next session): Written review and scores of two peer grants, and light review of six more aims pages

November 1 | Mock Study Section on 8 prior year grants

• Lecture: Biosketch (20 minutes)
• Exercise (full group): brainstorm 3-7 contributions to science (10 min)
• Exercise: faculty and senior grad students will guide students through a mock study section of 3-4 anonymized peer grants from prior years (60 min).
• Assignment (due Monday at noon, prior to next session): Polished Aims + Revised Research Strategy + Draft Biosketch + Revised F2 Background, Goals for Training + Revised F6 Selection of Sponsor + Revised F9 Sponsor and Co-Sponsor statements (**) + Draft Bibliography + A copy of one of mentor’s documents from each of the sections (** below)

November 15 | The ad minutia

• Lecture: F5. Respective Contributions; F11. Equipment**; F14. Vertebrate animals (if used)**; F16. Resource Sharing Plan**; F18. Authentication of Key Biological and/or Chemical Resources**; F11. Description of Institutional Environment and Commitment to Training; F15. Select Agent Research (if used)**; Narrative; Summary
• Exercise: Creating a summary and narrative from an aims page
• Assignment (due Monday at noon, prior to next session): ALL sections of the grants, adding tags to sections you want input on

November 29 | Wrap up and submission party

• Exercise: Co-writing session to finalize any remaining sections

Note: After each session, following a coffee break, the students are encouraged to use the next 60-90 minutes as dedicated writing time with faculty and peer mentors available for on-the-spot feedback (encouraged but optional). We will provide space and coffee for this.

NanoMaster: Judith Golden | jgolden@wustl.edu

Synopsis

The perception of pain serves the vital function of providing information about potential or actual injury. The International Association for the Study of Pain (IASP) defines pain as “An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.” Because pain is inherently aversive, it serves the function of limiting tissue damage when a noxious stimulus is encountered. In contrast, a number of chronic pain conditions involve pain that persists in the absence of injury. It has been estimated that 100 million adults suffer from chronic pain in the United States, accounting for an expenditure of approximately 600 billion dollars in pain related patient care. Current pharmacological treatments for pain management are sub-optimal, and significant adverse effects limit their use. Consequently, there is significant motivation to develop new approaches to treat pain. There are no pre-requisites for this Nano.

Learning objectives

The objective of this nano-course is to provide an understanding of the nervous system pathways that transmit and modulate pain and of the methodology used to study pain in rodents and humans. The course will cover the anatomy of peripheral and central pain pathways and the physiology of pain transmission, transduction and modulation. In addition, we will discuss human pain conditions and evaluation of pain in human subjects. Experimental approaches used to evaluate pain in rodents will also be discussed. We will include discussion of relevant literature (recent and classic papers) in each session.

Assignments/evaluation

Students will be evaluated based on class participation and attendance.

September 6
Dr. Kate Gurba and Dr. Lara Crock

• Human Pain: Prevalent conditions; Evaluation of pain in human subjects

September 13
Dr. Judy Golden

• History of Pain Research
• Anatomy: Primary sensory neurons, Nociceptor diversity, Spinal cord, Pain Pathways

September 20
Dr. Simon Haroutounian

• Human Pain: treatment

Dr. Meaghan Creed

• Modulation of Pain: Descending pathways, Affective Co-morbidities, Abuse/Reward, Depression/Anxiety

September 27
Dr. Kathryn Braden

• Physiology: Primary sensory neurons, Nociceptors, Spinal cord, Supraspinal centers

October 4
Dr. Meaghan Creed, Dr. Judy Golden, Dr. Kathryn Braden

• Injury: Peripheral Sensitization, Central Sensitization, Theories of Pain

October 11
Dr. Meaghan Creed, Dr. Judy Golden, Dr. Kathryn Braden

• Pain Research Methods: Behavior, In vitro and in vivo physiology

NanoMaster: Geoff Goodhill, PhD | g.goodhill@wustl.edu

Synopsis

Larval zebrafish have now become a key vertebrate model system in systems neuroscience research. The powerful combination of their genetic tractability, rapid development, accessibility for non-invasive imaging of neural activity up to whole-brain scale, and complex behavioral repertoire make them ideal for addressing a wide range of questions. These include how functional neural circuits develop, how neural circuits subserve behavior, and how mutations correlated with human diseases alter neural circuit development and function. In this course, we will explore the cutting edge of research in addressing these questions using zebrafish models, and learn how methodologies such as big data analysis and computational modeling have been applied in this case. The course will be primarily readings-based, with the focus on discussing recent research. There are no pre-requisites for this Nano.

Learning objectives

• Understand basic experimental and mathematical tools used to image and analyze neural activity from large populations of neurons.
• Understand some experimental and mathematical methodologies for analyzing complex behaviors.
• Understand basic principles of zebrafish systems neuroscience.
• Learn about some current frontiers in deriving insights into behavior and brain function from zebrafish models.

Assignments/evaluation

One or more primary literature articles/reviews will be discussed during each session. Prior to each session, students will have read the assigned articles and turn in a short pre-class writing assignment (3-5 questions to be answered at home). Each session quiz will contribute 15% of the final grade. The remaining 10% are contingent on filling out the Course Evaluation.

October 3
Dr. Takeshi Yoshimatsu

• Systematic behavioral analysis

October 10
Dr. Takeshi Yoshimatsu

• Studying higher cognitive functions in larval zebrafish

October 17
Dr. Martha Bagnall

• Development of movement and locomotion

October 24
Dr. Martha Bagnall

• Neuromodulation and motor control

October 31
Dr. Geoff Goodhill

• Central circuits underlying prey hunting (Halloween special!)

November 7
Dr. Geoff Goodhill

• Brain-wide information processing

NanoMaster: Yao Chen, PhD | yaochen@wustl.edu

Synopsis

This course will discuss how chemical neuromodulators (e.g., dopamine, acetylcholine, neuropeptides) transform behavior via molecular, synaptic, and circuit changes, and how their mis regulation leads to diseases. We will focus on how the effects of neuromodulators across these different levels relate to each other and discuss whether and how we can build a framework of neuromodulator actions across different levels. In each of the first four sessions, we will cover the fundamentals, discuss a classical paper, and a recent paper, with a focus on critical thinking and identifying unsolved mysteries in neuromodulation. In the last two sessions, students will form teams to brainstorm and present unsolved mysteries in the field: what do we know, what are the challenges, and what are potential ways to address these challenges.

Learning objectives

• Learning knowledge: the effect of neuromodulators at the molecular, synaptic/cellular, circuit, and behavior level.
• Appreciating history: learning how we gained current knowledge by reading classical papers
• Identifying challenges and opportunities in the field of neuromodulation
• Appreciation and enhancing skills in teamwork and presentations
• Enhanced ability of critical thinking

Assignments/evaluation

The students will be given pass/fail. Evaluation will be based on class participation and small group discussions.

January 19
Dr. Yao Chen

• Neuromodulator actions on receptors and intracellular signals

January 26
Dr. Meaghan Creed

• Neuromodulator actions on synapses and cells

February 2
Dr. Marco Pignatelli

• Neuromodulator actions on neural circuits

February 9
Dr. Meaghan Creed and Dr. Marco Pignatelli

• Neuromodulator actions on behaviors and diseases

February 16
Students led, all instructors

• Unsolved Mysteries in Neuromodulation

February 23
Students led, all instructors

• Unsolved Mysteries in Neuromodulation

NanoMaster: Joshua Siegel, MD, PhD | jssiegel@wustl.edu

Synopsis

The focus on this nano-course is to understand how rapid antidepressants change the brain, spanning from the molecular up to the systems and psychological level. The recent discovery of ketamine and psychedelics as rapid acting antidepressants has opened new doors to understanding how, when, and why drugs can treat depression. Antidepressants activate a number of signal transduction pathways that lead to increased neuroplasticity (neurogenesis, neuritogenesis, synaptogenesis) in the hippocampus and prefrontal cortex. These pathways are suppressed in stress and are stimulated by many classes of antidepressants. Blocking these pathways prevent antidepressants from working. Most recently, psychedelics have been found to rapidly and powerfully stimulate these neurotrophic pathways. This young field is of critical importance to medicine and society.

Learning objectives

• Session 1: Review the pharmacology and mechanism of antidepressant medications, examine off-target effects, toxicity, and withdrawal; and discuss clinical management of antidepressants
• Session 2: Understand the Neurotrophic hypothesis and the mechanism of ketamine (NMDA receptor pathway) and clinical data
• Session 3: Understand the history, neuropharmacology, clinical efficacy, safety, antidepressant mechanism of psychedelics
• Session 4: Understand the history, neuropharmacology, clinical efficacy and mechanisms of neurosteroids
• Session 5: Understand model organisms used to study antidepressant mechanisms – techniques, strengths, limitations
• Session 6: Understand the meso- and macro-scale effects of ketamine and psychedelics which correspond to their acute mind-altering effects.

Assignments/evaluation

Student groups will be assigned to present an article each week. Students will be graded on attendance and their ability to understand and critically review a relevant scientific article.

February 2
Dr. Brendan O’Connor

• Intro to Antidepressant Pharmacology – Monoamines

February 9
Dr. Subha Subramanian

• The Neurotrophic Hypothesis and Ketamine | Reading: Autry et al., 2011

February 16
Dr. Joshua Siegel

• Psychedelics | Reading: Cameron et al., 2020 & Yaden & Griffiths 2020

February 23
Dr. Steve Mennerick

• Neurosteroids | Reading: Reading: Antonoudiou et al., 2022

March 1
Yang-Yang Feng, MSTP student (Dr. Monosov lab)

• Model organisms for studying depression| Reading: Alexander et al., 2019

March 8
Dr. Joshua Siegel

• Neuroimaging Studies of Psychedelics| Reading: Carhart-Harris et al., 2016

NanoMaster: Gaia Tavoni, PhD | gaia.tavoni@wustl.edu

Synopsis

We will provide an introduction to several topics in theoretical and computational neuroscience including biophysical and dynamical modeling of neural circuits, optimization of circuit models from data and top-down hypotheses, statistical and information-theoretic analyses of neural networks, and the application of computational and behavioral analyses to uncover the underlying breakpoints in disorders of cognition. The course will include high-level discussions of methods and research papers relevant to these topics.

Learning objectives

• Topic 1: Statistical and information-theoretic analyses of neural networks.
  • Part I: Graphical models and statistical inference. Probabilistic graphical models are a powerful tool to interpret the activity of populations of neurons. They define the probability of multi-neuron activity patterns from a graph of statistical interactions, which can be reconstructed from neural data. There are stationary and non-stationary models, which include maximum-entropy (e.g., Ising) and generalized linear models. Students will learn several applications of these models to neuroscience.
  • Part II: Information theory for neuroscience. Information theory provides statistically rigorous tools with wide applicability in neuroscience, including particularly understanding early sensory coding. Students will learn the definition and meaning of information, entropy, mutual information, and some applications of information theory to the study of efficient coding in single neurons and neuronal populations.

• Topic 2: Modeling for hypothesis and prediction generation.
  • Part I: Biophysical modeling of circuit effects of general anesthesia. This class will cover how biophysical modeling may be used to generate hypotheses regarding mechanisms underlying changes in brain electrophysiology. To center the discussion, we will use the example of general anesthesia, which produces bulk effects on macro-scale neural activity, such as measured by electroencephalography. We will describe several examples of how voltage-gated conductance models, as well as mean-field models, can be used to both describe such effects and hypothesize as to their circuit underpinnings.
  • Part II: Optimization of neural circuits from data and top-down hypothesis. This class will cover how algorithmic optimization strategies can be used to parameterize (i.e., “fit”) mathematical circuit models to data, and cover the explanatory value of such modeling. In addition, we will also discuss how formal analytical optimization can be used to generate circuit models that are responsive to mathematical objective functions, and how such models themselves constitute hypotheses that ascribe functional salience to specific neural architecture and dynamics.

• Topic 3: Applications in psychiatry.
  • Computational neuroscience has become an important tool in the clinic. This will be discussed in this concluding lecture. We will discuss how computational psychiatry has been used to further understand the breakpoints in the behavioral algorithms of clinical populations. Special attention will be paid to OCD and depression, and how sophisticated behavioral and computational approaches have begun to shed light on their underlying neural mechanisms.

Assignments/evaluation

• Students will be asked to take a short quiz at the end of each session.

February 5 (Topic 1)
Dr. Gaia Tavoni

• Graphical models and statistical inference

February 7 (Topic 1)
Dr. Gaia Tavoni & Dr. Geoffrey Goodhill

• Information theory for neuroscience

February 9 (Topic 2)
Dr. ShiNung Ching

• Biophysical modeling of circuit effects of general anesthesia

February 12 (Topic 1)
Dr. Geoffrey Goodhill

• Information theory for neuroscience (continued)

February 16 (Topic 2)
Dr. ShiNung Ching

• Optimization of neural circuits from data and top-down hypothesis

February 19 (Topic 3)
Dr. Ilya Monosov

• Applications in psychiatry

NanoMaster: Thomas Papouin, PhD | thomas.papouin@wustl.edu

Synopsis

This course will focus on the fast-growing area of glia research. Through reading and discussing primary literature, students will debate emerging concepts surrounding glial heterogeneity, glia excitability, and the roles of glia in development, brain function, and disease. Sessions will include discussions guided by experts currently engaged in glia research, in order to provide students with a source of knowledge and perspective on the subject. Through attending the course, students will gain a broader appreciation for the multi-cellular underpinnings of brain function, capture key emerging concepts in a trendy area of Neuroscience, and gather ideas for their own research. There are no re-requisites for this Nano.

Learning objectives

• Participants will learn about the role of glia in development, health, and disease.
• Participants will become more familiar with the different types of glial cells, their roles, how they sculpt the nervous system connectivity and function, and how their activity is shaped by various contexts.
• Participants will learn about the broad set of techniques used to probe the roles and diversity of glial cells in the CNS/PNS
• Participants will connect with experts and other learners interested in research on glia.
• Participants will critically evaluate the latest literature on glia, as well as historical perspectives, and emerging trends.

Assignments/evaluation

During each session, one (or more) primary literature articles/reviews will be discussed. Prior to each session, students will have read the assigned article(s) and will turn in a short pre-class writing assignment (3-5 questions to be answered at home). Each session quiz will contribute 15% of the final grade (15 x 6 sessions = 90%). The remaining 10% are contingent on filling out the Course Evaluation.

March 25 (Monday)
Dr. Jason Ulrich

• Glial Genetics in Health and Disease

March 29th (Friday)
Dr. Sarah Ackerman

• Glia as Architects of Nervous System Development

April 1 (Monday)
Dr. Thomas Papouin

• Are Astrocytes Excitable? A Peek into Astrocyte Calcium Signaling

April 5 (Friday)
Dr. Thomas Papouin

• What Do Astrocytes Really Do?

April 8 (Monday)
Dr. Erik Musiek

• Glia in Neurodegeneration

April 12 (Friday)
Dr. Robyn Klein

• Glia in Neuroinfectious Disease

NanoMaster: Guoyan Zhao, PhD | gzhao@wustl.edu

Synopsis

‘Omic’ technologies are aimed at the universal detection of genes, their regulation and functions (genomics), mRNA (transcriptomics), proteins (proteomics) and metabolites (metabolomics) in a specific biological sample in a non-targeted and non-biased manner. Omic technologies have a broad range of applications and have recently emerged as powerful tools to define hypotheses that can be further tested.
We are at the beginning of a new era where these techniques are becoming standards and routinely applied in broad research areas to answer a variety of biomedical questions. However, technology is moving faster than ever before, and data analysis is complex as a huge amount of data is generated. What are the available technologies and what is the best tool for data analysis? This nano-course will provide participants with both the knowledge and practical skills required to perform basic transcriptomic and proteomic data analysis. There are no re-requisites for this Nano. However, the learning outcome may depend on the experience of the participant.

Learning objectives

This nano-course will provide an understanding of the current available transcriptomics and proteomics technologies, and resources for data analysis. At the end of the course, participants will learn about the broad set of cutting-edge genomic technologies and their pros and cons. They will be equipped with the knowledge to determine which technology to choose from and the tools/resources to further develop their knowledge. Participants will connect with experts and other learners using similar technologies.

Assignments/evaluation

During each session, one (or more) primary literature articles/reviews will be discussed or participants will work on data analysis using example datasets. Prior to each session, students will have read the assigned article or training material and will turn in a short pre-class writing assignment over the paper or training material (3-5 questions to be answered at home). The assignments will contribute 15% of the final grade (15 x 6 sessions = 90%). The remaining 10% are contingent on filling out the Course Evaluation.

April 5
Dr. Guoyan Zhao

• From RNA-seq to single-cell technology: outline of the goals of the course, RNA-seq technology development and the current state of single-cell technology, bulk RNA-seq data analysis workflow and hands-on practice

April 12
Dr. Guoyan Zhao

• Introduction to data analysis for scRNA-seq and hand on practice

April 19
Dr. Tristan Li

• Single-cell genomic meets glia biology

April 26
Dr. Dennis Goldfarb

• Mass spectrometry-based proteomics

May 3
Dr. Dennis Goldfarb

• Mass spectrometry-based proteomics data analysis

May 10
Dr. Shamim Mollah

• Multiomics data integration