"Small Brains, Big Ideas: the Value of Model Organisms to Science”

"Small Brains, Big Ideas: The value of model organisms to science”

Dr. Yuly Fuentes-Medel Executive Director Descience 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 What is a model organism? An experimental system used to study a fundamental problem, such as a disease

Fish Mice Worm Fly

hp://philadams.co/wp-content/uploads/2012/02/yeast1.jpg hp://testweb.science.uu.nl/developmentalbiology/images/adult_worm.jpg Yeast hp://thumbs.dreamsme.com/z/fruit-ﬂy-single-drosophila-melanogaster-white-background-34306446.jpg hp://www.renalgenes.org/zebraﬁsh.jpg hp://cdni.wired.co.uk/1920x1280/k_n/Mouse_2.jpg

Model organisms help us study complex problems 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-3

http://web.mit.edu/horvitz/www/peoplelinks/current.html http://www.wormbook.org/chapters/www_programcelldeath/pcdfig1.jpg Cell Death Wingless is a conserved gene that led to solutions to human diseases Fly Human Wg Wg

B-catenin pathway

http://amapress.gen.cam.ac.uk/?p=1191 http://en.wikipedia.org/wiki/Drosophila_melanogaster 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 2001 http://www.ijdvl.com/articles/2011/77/3/images/ijdvl_2011_77_3_403_79746_f1.jpg Choice of organism should be driven by the problem that you deﬁne

Consciousness Memory formation

Lymphoid Programmed Cell http://thealchemicalegg.com/X.GIF development http://24.media.tumblr.com/tumblr_me026d6jry1qf252bo1_r1_1280.jpg http://3.bp.blogspot.com/-e9ayhUJ0ZYc/UTDYwOgt4WI/AAAAAAAAcMY/PgqfIcriJ7k/s1600/white-laboratory-mouse.jpg Death http://www.mpg.de/4377505/zoom.jpg

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 Model organisms also have brains

hp://testweb.science.uu.nl/developmentalbiology/images/adult_worm.jpg hp://home.physics.ucla.edu/~arisaka/home/CElegans/ﬁles/stacks_image_105.jpg hp://stephenesherman.com/wp-content/uploads/2012/10/drosophila12.jpg hp://www.kurzweilai.net/decoding-the-human-brain-with-help-from-a-ﬂy

To understand the brain we need to understand synapses

Synapse Neuromuscular Junction NMJ Why can we study brain problems using fruit ﬂies?

• ﬂies possess 77% of human genes linked with diseases

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC311089/#!po=2.94118 How do we study genetic changes?

normal vs mutant

https://diogenesii.files.wordpress.com/2010/07/lewis-16.gif Drosophila as a model to study synapses

• short generation time (~10 days)

• extremely sophisticated genetic system

• co$t: relatively inexpensive Drosophila Life cycle

http://hiscience.com/aramblog/wp-content/uploads/2013/01/life_cycle.jpg Larvae also have a brain and deﬁned neural circuits

http://www.prokop.co.uk/Research/Drosi-Info/Synapse-location.html 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.) Synapses can be visualized as synaptic boutons

neuron / muscle

neuron / muscle Precursors of synapses can be observed live under a microscope

0 hr

24 hr Synapses are dynamic structures

PLoS Biol 7(8): e1000184. doi:10.1371/journal.pbio.1000184 http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1000184 C. elegans CED-1 is required for engulfment of cell corpses

CED-1

cell corpse

NPXY

engulﬁng cell engulfment Does Draper signaling work to support maintenance of synapses?

Draper

Synapses?cell corpse

NPXY

ITAM

engulfment Draper mutants accumulate presynaptic debris and ghost boutons

PLoS Biol 7(8): e1000184. doi:10.1371/journal.pbio.1000184 http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1000184 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): e1000184. doi:10.1371/journal.pbio.1000184 http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1000184 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 INTERMISSION

Questions? Model organisms are a cheaper way to do science

Generation # off spring Doubling Space Organism time time C. elegans 3 days 300 10 hrs 3 ft3 Drosophila 10 days 250 2 days 30 ft3 Mouse 3 months 4 1.5 months 1/2 LZR

Humans 25 years 1-2 75 years Boston 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.

http://www.nature.com/polopoly_fs/1.15393!/menu/main/topColumns/topLeftColumn/pdf/510202a.pdf 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

http://www.nature.com/polopoly_fs/1.15393!/menu/main/topColumns/topLeftColumn/pdf/510202a.pdf 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

http://www.nature.com/polopoly_fs/1.15393!/menu/main/topColumns/topLeftColumn/pdf/510202a.pdf

VIDEO http://www.youtube.com/watch?v=c_xPX-QAmuw www.smallbrains.org VIDEO 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