Stephen D. Larson NeuroML Workshop 03/13/12. Enter the worm: c. elegans I’ve only got 1000 cells in my whole body… please simulate me!

Slides:



Advertisements
Similar presentations
THE WORM Caenorhabditis elegans as a model organism.
Advertisements

What is a Cell?
OpenWorm Extended Research Timothy Busbice, 12/31/2012 History For the past 20+ years, I have tried to create a connectome using individual programs to.
Chair: Angus Silver University College London INCF - Neuroinformatics 2014 WORKSHOP 4 Open collaboration in computational.
1 Harvard Medical School Mapping Transcription Mechanisms from Multimodal Genomic Data Hsun-Hsien Chang, Michael McGeachie, and Marco F. Ramoni Children.
Blue brain Copyright © cs-tutorial.com.
Presented by: SACHIN N 1GA07EC087 Under the guidance: B.C.DIVAKAR.
Nature Versus Nurture Neurons, The Brain and Nervous System Science 2 Fall 2014 Dr. Michael Sneary Neurons, The Brain and Nervous System Science 2 Fall.
Fungal Semantic Web Stephen Scott, Scott Henninger, Leen-Kiat Soh (CSE) Etsuko Moriyama, Ken Nickerson, Audrey Atkin (Biological Sciences) Steve Harris.
Synapse and Neurotransmitter Dr. Shaikh Mujeeb Ahmed Assistant prof. Physiology Al Maarefa College 1 Lecture slides are prepared by Dr.Mohammed Sharique.
WHS AP Psychology Unit 3: Biological Psychology Essential Task 3-1: Identify the basic parts of the neuron (dendrites, cell body, axon, terminal buttons,
Manolis Kellis Broad Institute of MIT and Harvard
4 th NeuroML Development Workshop & BrainScaleS CodeJam, Edinburgh, March NeuroML: Where are we at? Padraig Gleeson Department.
Topic 1: It’s My Body Part 2: Nervous System.
Honors Chemistry Review of basic concepts (ch.1).
Study guide…part 1 What are the three types of neurons? What is the structure of a neuron? How does saltatory conduction change the speed of the impulse?
Lis Nielsen, Ph.D. Division of Behavioral and Social Research (BSR) National Institute on Aging NIA/IPSR Workshop: Advancing Integrative.
Lesson Overview Lesson Overview Studying Life Lesson Overview 1.3 Studying Life.
AnimatLab: A Toolkit for Analysis and Simulation of the Neural Control of Behavior Ying Zhu Department of Computer Science Georgia State University SURA.
Molecular mechanisms of memory. How does the brain achieve Hebbian plasticity? How is the co-activity of presynaptic and postsynaptic cells registered.
AP Biology Nervous Systems Part 1.
Elements of Neuronal Biophysics The human brain Seat of consciousness and cognition Perhaps the most complex information processing machine in nature.
What is Biophysics? Biophysics is that branch of knowledge that applies the principles of physics and chemistry and the methods of mathematical analysis.
Brain Computer Interface
Mind, Brain & Behavior Wednesday January 29, 2003.
LECTURE CONNECTIONS 1 | Introduction to Genetics © 2009 W. H. Freeman and Company.
Investigate biophysical, molecular and cellular mechanisms of synaptic transmission and plasticity under normal and pathological conditions-link between.
Cellular Internet Cell to cell communication is essential in order for organisms to coordinate activities that develop, survive and reproduce Cell communication.
Systems Biology ___ Toward System-level Understanding of Biological Systems Hou-Haifeng.
Blue Brain Project Carlos Osuna, Carlos Aguado, Fabien Delalondre.
Workshop on Structural and Computational Proteomics of Biological Complexes.
Neurotransmission ISAT 351, Spring, 2004 College of Integrated Science and Technology James Madison University.
Aim #1 Engage community Highlight existing: modeling efforts strategic datasets Aim #2 Define and bootstrap an inclusive community-driven model and data-integration.
Copyright © 2009 Pearson Education, Inc. Neurons and Neurological Cells: The Cells of the Nervous System  The nervous system  Integrates and coordinates.
Introduction.  Complexities occurring even with simplest function ◦ Example.
COMPUTERS IN BIOLOGY Elizabeth Muros INTRO TO PERSONAL COMPUTING.
Biological Networks & Systems Anne R. Haake Rhys Price Jones.
The Cell The basic unit of all living things 1. Robert Hooke was the first to name the cell (1665) 2.
AP Biology Cell Communication. AP Biology Communication Methods  Cell-to-cell contact  Local signaling  Long distance signaling.
Susan Capasso, Ed.D., CGC St. Vincent’s College Suggested Lecture Presentation Copyright © 2009 Pearson Education, Inc. Chapter 7 Neurons: The Matter of.
Surveying the Chapter: Overview What We Have in Mind  Building blocks of the mind: neurons and how they communicate (neurotransmitters)  Systems that.
Organization of the Body. Overview of Anatomy and Physiology Anatomy – the study of the structure of body parts and their relationships to one another.
AP Biology Nervous Systems Part 1.
Neurons.
The Nervous System. Lesson objectives By the end of this lesson you should know: The difference between the CNS and the PNS The function of the nervous.
CHS AP Psychology Unit 3: Biological Psychology Essential Task 3-1: Identify the basic parts of the neuron (dendrites, cell body, axon, terminal buttons,
Neurons: Cellular and Network Properties
University of Pavia Dep. of Electrical, Computer and Biomedical Engineering Laboratory of Bioinformatics, Mathematical Modelling and Synthetic Biology.
Connectome Research Timothy Busbice, Updated: 03/10/2014 History For the past 20+ years, I have tried to create a connectome using individual programs.
KEY CONCEPT Entire genomes are sequenced, studied, and compared.
“Levels of Analysis in Behavioral Neuroscience”
Unit 3: Biological Psychology
An Integrative Approach to Psychopathology
Chapter 2 The Biological Basis of Behavior
Biology is the scientific study of life
Mental Functioning and the Gene Ontology
Padraig Gleeson CodeJam workshop, 28th January 2014
Unit 4: Biological Psychology
Nervous System Function
Unit 4: Neurobiology Lesson 2: Neurons
Nerve cell functioning
Ms. Scribner’s Biology class
Body Organization. Body Organization Learning Objectives: Identify terms relating to the organization of the body Describe the properties of life Label.
KEY CONCEPT Entire genomes are sequenced, studied, and compared.
Biological Psychology
3-1 Neurons Psychology Essential Task 3-1:
KEY CONCEPT Entire genomes are sequenced, studied, and compared.
Neuroscience and Behavior Notes 2-1 (obj 1-6)
Neurons: Cellular and Network Properties
Presentation transcript:

Stephen D. Larson NeuroML Workshop 03/13/12

Enter the worm: c. elegans I’ve only got 1000 cells in my whole body… please simulate me!

In search of nature’s design principles via simulation How can a humble worm regulate itself? – Reproduces – Avoids predators – Survives in different chemical and temperature environments – Seeks and finds food sources in an ever changing landscape – Distributes nutrients across its own cells – Manages waste and eliminates it If we can’t understand genes to behavior here, why would we expect to understand it anywhere?

Virtual physical organisms in a computer simulation

Closing the loop between a worm’s brain, body and environment Simulated World Detailed simulation of worm body Detailed simulation of cellular activity

The goal: understanding a faithfully simulated organism end to end Extracting mathematical principles from smaller biological systems is necessary if we are going to understand and reconstruct the much larger system of the human.

Outreach: put the model online and let the world play with it Sex: Hermaphrodite Interested in: Escaping my worm Matrix Relationship status: Its complicated.

Worm biology  ~1000 cells / 95 muscles  Neuroscience: 302 neurons 15k synapses  Shares cellular and molecular structures with higher organisms Membrane bound organelles; DNA complexed into chromatin and organized into discreet chromosomes Cell control pathways  Genome size: 97 Megabases vs human: 3000 Megabases.  C. elegans homologues identified for 60-80% of human genes (Kaletta & Hangartner, 2006)

Entire cell lineage mapped Christian Grove, Wormbase

Entire cell lineage mapped Christian Grove, Wormbase

Entire cell lineage mapped Christian Grove, Wormbase

Entire cell lineage mapped Christian Grove, Wormbase

Full connectome Varshney, Chen, Paniaqua, Hall and Chklovskii, 2011

P. Sauvage et al. / Journal of Biomechanics 2011 Biomechanics

Interrogation of Behavior Liefer et al., 2011

C. Elegans disease models Kaletta & Hengartner, 2006 Metabolic syndrome Diabetes and obesity Ageing Oncology Cancer Neurodegeneration Alzheimer’s disease Parkinson’s disease Huntington’s disease Neurobiology Depression Pain, neuronal regeneration Genetic diseases ADPKD Muscular dystrophy Ionchannelopathies Innate immunity

Can present drugs Kaletta & Hengartner, 2006

March– Sept 2011

Team – A brief history

Collaboration technologies used

Mechanical model Palayanov, Khayrulin, Dibert (submitted)

3D body plan Christian Grove, Wormbase

Core platform OpenWorm VizSimValOpt

One core hooks together multiple simulation engines addressing diverse biological behavior Core simulation platform Cellular motility Cellular metabolism Cell membrane excitability Synaptic transmission Sensory transduction

Estimates of computational complexity  Mechanical model ~5 Tflops  Muscle / Neuronal conductance model ~240 Gflops  One Amazon GPU cluster provides 2 Tflops Source:

NVIDIA Tesla drivers OpenCL JavaCL OSGi Simulation Engine Simulation engine libraries

Neuronal model GPU Performance Testing: 302 Hodgkin-Huxley neurons for 140 ms (dt = 0.01ms) Architecture proof of concept using Hodgkin-Huxley neurons ms

Worm Browser

Finite element modeling

Neuron models from Blender to NeuroML

Put the parts back together Open Worm Team, March 2012 Spatial model of cells converted to NeuroML Sergey Khayrulin Connections defined Tim Busbice + Padraig Gleeson Ion channel placeholders Tim Busbice + Padraig Gleeson Inferred neurotransmitters Dimitar Shterionov

Focus on a muscle cell

Case study: locomotion Gao et al, 2011

Muscle cell with “arms” Cell Body 5 arms, 10 compartments each, passive currents Cell body, 1 compartment, active currents Boyle & Cohen, 2007

Conductance model of c. elegans muscle cell Boyle & Cohen, 2007

Cell Body Quadrant 1Quadrant 2 Quadrants of muscle cells

Muscle cell roadmap

Physics: Smoothed Particle Hydrodynamics (SPH)

Progress with optimization Alex Dibert

Progress with optimization Alex Dibert

Progress with optimization Alex Dibert

Progress with optimization Alex Dibert

Current challenges  Better integration of genetic algorithms into simulation pipeline  Filling in the gaps of the ion channels for the spatial connectome  Multi-timescale integration of smoothed particle hydrodynamics and conductance based electrical activity of muscle cell

Multi-scale synthesis in c. elegans Motivated highly detailed simulations in a small, well studied organism Described the effort of a distributed “virtual team” of scientists and engineers Described early results in building a framework and engine for c. elegans simulation Described current opportunities for contribution