"Small Brains, Big Ideas: The value of model organisms to science. Dr. Yuly Fuentes-Medel Executive Director Descience

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1 "Small Brains, Big Ideas: The value of model organisms to science Dr. Yuly Fuentes-Medel Executive Director Descience

2 Outline 1. What is a model organism? 2. Big questions solved by small-brained organisms 3. Flies brains teach us about human brains 4. Inspiring science in emerging economies

3 What is a model organism? An experimental system used to study a fundamental problem, such as a disease Worm Fly Fish Mice Yeast h"p://philadams.co/wp- content/uploads/2012/02/yeast1.jpg h"p://testweb.science.uu.nl/developmentalbiology/images/adult_worm.jpg h"p://thumbs.dreams@me.com/z/fruit- fly- single- drosophila- melanogaster- white- background jpg h"p:// h"p://cdni.wired.co.uk/1920x1280/k_n/mouse_2.jpg

4 Model organisms help us study complex problems

5 Studying cell death in a worm sheds light on cancer Bid, Bax EGL-1 BCl-2 CED-9 Apaf-1 CED-4 Caspase-9 CED Cell Death

6 Wingless is a conserved gene that led to solutions to human diseases Fly Human Wg Wg B-catenin pathway

7 Example of how flies advanced our understanding of disease Tuberous sclerosis: flies to the rescue TSC1 and TSC2 tumor suppressors antagonize cell growth TSC1-/- control Gao and Pan, Genes Dev. 2001; Potter, Huang and Xu, Cell

8 Choice of organism should be driven by the problem that you define Consciousness Memory formation Lymphoid development Programmed Cell Death

9 Summary Model organisms are a powerful tool to study biology Genes discovered in model organisms have contributed to solving health problems Pick the right organism for your specific biological question

10 Model organisms also have brains h"p://testweb.science.uu.nl/developmentalbiology/images/adult_worm.jpg h"p://home.physics.ucla.edu/~arisaka/home/celegans/files/stacks_image_105.jpg h"p://stephenesherman.com/wp- content/uploads/2012/10/drosophila12.jpg h"p:// the- human- brain- with- help- from- a- fly

11 To understand the brain we need to understand synapses Synapse Neuromuscular Junction NMJ

12 Why can we study brain problems using fruit flies? flies possess 77% of human genes linked with diseases

13 How do we study genetic changes? normal vs mutant

14 Drosophila as a model to study synapses short generation time (~10 days) extremely sophisticated genetic system co$t: relatively inexpensive

15 Drosophila Life cycle

16 Larvae also have a brain and defined neural circuits

17 This is how synapses look under a microscope muscle neuron / muscle The Fly Neuromuscular Junction: Structure and Function, Volume 75: Second Edition (International Review of Neurobiology.)

18 Synapses can be visualized as synaptic boutons neuron / muscle neuron / muscle

19 Precursors of synapses can be observed live under a microscope 0 hr 24 hr

20 PLoS Biol 7(8): e doi: /journal.pbio Synapses are dynamic structures

21 C. elegans CED-1 is required for engulfment of cell corpses CED-1" cell corpse" NPXY" engulfment" engulfing cell"

22 Does Draper signaling work to support maintenance of synapses? Draper" " Synapses?" cell corpse" NPXY" ITAM" engulfment

23 Draper mutants accumulate presynaptic debris and ghost boutons PLoS Biol 7(8): e doi: /journal.pbio

24 Loss of Draper results in severely reduced NMJ growth continuous clearance is essential for normal NMJ growth synaptic debris interferes with NMJ growth PLoS Biol 7(8): e doi: /journal.pbio

25 Summary II To understand the brain we need to understand synapses Model organism genetics is a powerful tool to understand biology Synapses are dynamic structures An active molecular machinery creates the appropriate number of synaptic connections Cell death pathway is also important for neurons

26 INTERMISSION Questions?

27 Model organisms are a cheaper way to do science Organism Generation time # off spring Doubling time Space C. elegans 3 days hrs 3 ft 3 Drosophila 10 days days 30 ft 3 Mouse 3 months months 1/2 LZR Humans 25 years years Boston

28 There is a significantly lower amount of investment in science in Latin America USA average of investment on research is about of 2,8% of their GDP. In contrasts, Brazil invest an average of 1,1 % of the GDP While, Argentina, Chile, Ecuador, Colombia, Paraguay, Bolivia are invest an average of only 0,5% of their GDP.

29 There are significantly fewer scientists in Latin America USA has about 10 scientist per 1,000 labor force China 1,8 Argentina 3 Brazil 1,8 Uruguay 0,5 Chile 0,6 Venezuela 0,3 Bolivia 0,2 Colombia 0,2 Ecuador 0,2 Paraguay 0,05

30 HOWEVER, there are some heroes that manage to produce science in Latin America Brazil 46,306 has published papers in 2013 Argentina 9,337 Chile 6,794 Bolivia 222 Peru 1,004 Colombia 4,556

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35 VIDEO

36 Thank you! SITN would like to acknowledge the following organizations for their generous support. Harvard Medical School Office of Communications and External Relations Division of Medical Sciences The Harvard Graduate School of Arts and Sciences (GSAS) The Harvard Graduate Student Council (GSC) The Harvard Biomedical Graduate Students Organization (BGSO) The Harvard/MIT COOP

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