An Educational Journey Leading to a

Career in ScienceUniversity of Wisconsin—Whitewater April 12, 2010

Curiosity is the Engine that Drives Science

United States of AmericaLongmont, Colorado (1984)

Longmont Junior High School

7th Grade (1984)Longmont, Colorado

8th Grade (1985)

Martin Luther KingMiddle School

St. Petersburg, Florida

LakewoodHigh School

9th &10th Grade (1986 & 87)

St. Pete High School

10-12th Grade (1987-89)

The Pointer Institute St. Pete Beach Hotels

Hao Wah ChineseRestaurant

Georgia Institute of Technology (1990)

Aerospace EngineeringPhilosophyChemical EngineeringHoechst Celanese

Pathfinder landing

Chemistry

1997

1990

1994

Peter G. Schultz

Andrew Wiles, Princeton

Chuck Thacker, UC BerkeleyJames Gunn, Princeton

1998

Irving Sigal PostdoctoralFellowship

Gary B. Schuster

UC Berkeley (1998) 1998Student demonstration

Free expressionAndrew Martinez (a.k.a. The Naked Guy)

A homeless man

The Scripps Research Institute

Torrey Pines Golf Course

Scripps

Black Beach

(1999-2001)

Miramar Air Station

San Diego Naval Station

Publication of the Aging Work

Progeria

Werner Syndrome

Hayley Okines

Hayley’s preparing for her best friend’s funeralhttp://www.youtube.com/watch?v=Kmb-XkSQg4cA tribute to children with Progeriahttp://www.facebook.com/profile.php?v=app_2309869772&id=100000381621440

Carnegie Mellon UniversityAssistant

Professor, 2001Chemistry Department Research Interests

Addressing problems at the interface of Chemistryand Biology, with emphasis on gene regulation

and correction

Discovery of the Genetic Codes

1944

1953 1954

2001

DNA Recognition

WC base-pairing DNA Double Helix

Nucleic Acid Recognition

Recognition

Frank-Kamenetskii, M.D. Nature, 1987, 328, 17.

Groove BindingTriplex-Formation

Polydactyl Zinc-Fingers

N

NN

N

N

Sugar

H HN N

O

Sugar

O

H

NNSugar O

O H

NN

N

O

H

N

H

H

Sugar

N N

N

O

Sugar

H

HNN N

HO

SugarH

HC+

T

T

C

G

NH

N

N

OON

NH2N

NH2

O

H

H3C

H3C

H

N

CH3

N

HH

O

Distamycin

NH

N

N

OON

NN

O

H

H3C

H3C

HCH3

H3C

H N

N

CH3

2-Imidazole Netropsin (2-ImN)

Polyamides

Kielkopf and Dervan. Science, 1998, 282, 111.

Fregeau and Lown. JACS, 1995, 117, 8917.

Hoogsteen pairings

Jantz and Berg. Chem. Rev. 2004, 104, 789.Beerli and Barbas. Nat. Biotech, 2002, 20, 135.Pavletich, N. P. and Pabo, C. O. Science, 1991, 252, 809.

Lyamichev, V.I., Mirkin, S.M., Frank-Kamenetskii, M.D. J. Biomol. Struct. Dyn. 3, 1985, 327−338. Moser and Dervan. Science, 1987, 238, 645. Sun and Helene. Curr. Opin. Struct. Biol., 1993, 3, 34. Thuong and Helene. Angew. Chem. Int. 2003, 32, 666.

Caltech teamMIT, Johns Hopkins, Scripps teams

Paris team

Watson-Crick Recognition of Double-Stranded B-DNA

CMU team Dragulescu-Andrasi, A., Rapireddy, S., Frezza, B. M., Gayathri, C., Gil, R. R., Ly, D. H. J. Am. Chem. Soc., 2006, 128, 10258. Rapireddy, S., He, G., Roy, S., Armitage, B. A., Ly, D. H. J. Am. Chem. Soc., 2007, 129, 15596. Chenna, V., Rapireddy, S., Sahu, B., Ausin, C., Pedroso, E., Ly, D. H. ChemBioChem 2008, 9, 2388. Sahu, B., Chenna, V., Lathrop, K. L., Thomas, S. M., Zon, G., Livak, K. J., Ly, D. H. J. Org. Chem. 2009, 74, 1509. He, G., Rapireddy, S., Bahal, R., Sahu, S., Ly, D. H. J. Am. Chem. Soc., 2009, 131, 12088.

The infamous quotes:• “If you sleep well at night, you are not doing important science”• “There is no second place in science”• “If you’ve been to hell, everything else afterward is nirvana”

First Impressions on the Job Felt a sense of awe

Felt like walking on a tight-rope without the safety net beneath The BIGGEST fear was that I might ruin the lives of these young graduate students & postdocs

A Career in Science

Industry AcademiaPros Comfortable life (9-5 job) Higher (initial) salary Receive other financial incentives Deliver goods directly to consumers

Cons Follow company’s hierarchical rules Work is dictated by profit Job insecurity

Pros Academic freedom You are your own boss Opportunity to shape the lives of young people College tuition incentive for your children Job security (tenured)

Cons Constantly writing grant proposals Work long hours A lot more external obligations

Securing an Academic JobHiring

Stiff competition Selection is based on merit Invitation for interview Give a “chalk talk”, m/w colleagues Make an offer to the best candidate

Start-Up Package Laboratory space Start-up account

Tenure (5th or 6th yr)(1) Put together a tenure package (PI) -Scholastic achievements -Educational accomplishments -Departmental/university obligations -A list of students and colleagues(2) Dept. solicits letters from students, colleagues both internal & external (natl. & intl.)(3) Departmental level(4) Adhoc tenure committee(5) College level (dept. heads)(6) College deans & Provost(7) Board of Directors(8) President sends out the verdict

Philosophy on Education and on Life

Students learn best when they are inspired Schooling is about learning on how to learn Tackle each problem with fervor and conviction In life work hard, play hard—NO REGRET Take on personal misfortunes as challenges, not as excuses

GRADES will not matter in real life

A Measure of Success It’s NOT about fame or fortune

It’s about finding something in life that you are passionate about It’s about setting milestones and do everything you can to achieve them Even if you don’t succeed, you should be happy knowing that you have given your best Each one of us has different dreams and ambitionsMy definition of success A hardworking, honest, considerate, and responsible person I strive to be a better person each day than the day before Live your life according to your principles and values; there’s a proverb in my country that says “At HOME we have separate mothers, but in the FOREST there is only ONE mother” Be a big BROTHER or SISTER to those in need; take them under your wings and provide them with directions and guidance

A career goal: Dedicated towards improving human healthA personal goal: Restore the hopes and dreams of children around the world

Concluding Remarks

The future is a blank slate Find something in life that you are passionate about Mold it, shape it in any which way or form you like Make this world a better place for our children to live in The road may be long and treacherous, but you will get there if you are determined

Danith H. Ly, Department of Chemistry, Carnegie Mellon Universityhttp://www.chem.cmu.edu/groups/ly/

Acknowledgements

Collaborators:Professor Bruce ArmitageProfessor Alan WaggonerProfessor Joanne Yeh (Pitt)Professor Enrique Pedroso (Spain)Dr. Gregory FisherDr. Marcela MadridDr. Roberto GilDr. Jennifer Grandis (UPMC)Dr. Sufi Thomas (UPMC)Dr. Charles Thornton (RMC)Dr. Jerry Zon (ABI)Dr. Kenneth Livak (ABI)

Funding:Berkman Faculty Development FundCMU Innovative Seed FundApplied BiosystemsHead and Neck SPORES (NIH)Lung Cancer SPORES (NIH)National Institutes of Health

Postdocs:Miaomiao WangSrinivas RapireddyVenugopal ChennaBichsmita Sahu

Graduate students:Peng ZhouAnca Dragulescu-Andrasi (Stanford)Gaofei He Subhadeep Roy (Univ. Colorado)Matthew CrawfordIulia SacuiRaman Bahal

Undergraduate students:Lei Due (Penn State)Brian Frezza (Scripps Research Institute)Jihoon Lee (U Florida)Elizabeth Wiltrout (U Chicago)Jesse O’Hara (Princeton)Andy Hsieh (UC Berkeley)Brian Belardi (UC Berkeley)Robert Meehan (Yale)Sheldon Cheung (Caltech)