An Educational Journey Leading to a Career in Science

University of Wisconsin—Whitewater April 12, 2010

Curiosity is the Engine that Drives Science

United States of America Longmont, Colorado (1984)

Longmont Junior High School Martin Luther King Middle School Lakewood High School 7 th Grade (1984) Longmont, Colorado St. Pete High School 8 th Grade (1985) St. Petersburg, Florida The Pointer Institute 9th&10th Grade (1986 & 87) Hao Wah Chinese Restaurant St. Pete Beach Hotels 10-12th Grade (1987-89)

1990

Georgia Institute of Technology (1990)

Aerospace Engineering Philosophy Chemical Engineering Hoechst Celanese 1997 Pathfinder landing 1994 Gary B. Schuster Irving Sigal Postdoctoral Fellowship Peter G. Schultz Andrew Wiles, Princeton James Gunn, Princeton Chuck Thacker, UC Berkeley 1998 Chemistry

Student demonstration

UC Berkeley (1998)

1998 Free expression Andrew Martinez (a.k.a. The Naked Guy) A homeless man

The Scripps Research Institute (1999-2001)

Torrey Pines Golf Course Scripps Black Beach 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 funeral http://www.youtube.com/watch?v=Kmb-XkSQg4c A tribute to children with Progeria http://www.facebook.com/profile.php?v=app_2309869772&id=100000381621440

Carnegie Mellon University Assistant Professor, 2001 Chemistry Department Research Interests

Addressing problems at the interface of Chemistry and Biology, with emphasis on gene regulation and correction

Discovery of the Genetic Codes

1953 1954 1944 DNA Recognition 2001

Nucleic Acid Recognition

WC base-pairing DNA Double Helix Recognition Frank-Kamenetskii, M.D.

Nature

,

1987

,

328

, 17.

Groove Binding

MIT, Johns Hopkins, Scripps teams

Polydactyl Zinc-Fingers

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.

Paris team

Triplex-Formation

Sugar N

T

N O

Hoogsteen

H O N

pairings

Sugar N H N H N N O H N

T

O N Sugar H Sugar N

C+

N H N H N H O H

C

O N N Sugar N N H O

G

Sugar N N H 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

.

Caltech team

2003

, 32, 666.

Polyamides

O H 3 C N O H 3 C N N H H 2 N N H NH 2

Distamycin

N H O CH 3 N H N H O H 3 C N H CH 3 N H 3 C O H 3 C N N H O N H N H O N CH 3 N

2-Imidazole Netropsin (2-ImN)

Kielkopf and Dervan.

Science

,

1998

, 282, 111.

Fregeau and Lown.

JACS

,

1995

,

117

, 8917.

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 Pros  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 Academia 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 Job

    Hiring  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 (5 th or 6 th 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 ambitions  My 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 health A 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 University http://www.chem.cmu.edu/groups/ly/

Acknowledgements

Postdocs: Miaomiao Wang Srinivas Rapireddy Venugopal Chenna Bichsmita Sahu Graduate students: Peng Zhou Anca Dragulescu-Andrasi (Stanford) Gaofei He Subhadeep Roy (Univ. Colorado) Matthew Crawford Iulia Sacui Raman Bahal Collaborators: Professor Bruce Armitage Professor Alan Waggoner Professor Joanne Yeh (Pitt) Professor Enrique Pedroso (Spain) Dr. Gregory Fisher Dr. Marcela Madrid Dr. Roberto Gil Dr. Jennifer Grandis (UPMC) Dr. Sufi Thomas (UPMC) Dr. Charles Thornton (RMC) Dr. Jerry Zon (ABI) Dr. Kenneth Livak (ABI) 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) Funding: Berkman Faculty Development Fund CMU Innovative Seed Fund Applied Biosystems Head and Neck SPORES (NIH) Lung Cancer SPORES (NIH) National Institutes of Health