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Women In Science

Women In Science. Outlook Good – Medical schools, Vet Schools > parity Outlook OK – Dental Schools = Women gaining ground for parity, still some work to do (2002 = 40% female in National Dental Schools, 50% at MCG)

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Women In Science

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  1. Women In Science • Outlook Good – Medical schools, Vet Schools > parity • Outlook OK – Dental Schools = Women gaining ground for parity, still some work to do (2002 = 40% female in National Dental Schools, 50% at MCG) • “Glass ceiling” still applies – fewer women than predicted hold tenured positions, fewer are full professors • Reasons vary – career interruptions due to pregnancy still problematic • Still some male-dominated areas (eg., engineering, math, chemistry) where improvements can be made at both entry and advanced levels

  2. The 2009 Graduating Class of the Medical College of Georgia School of Dentistry

  3. UGA Vet School Stats

  4. Know What Makes A Difference • Excellent GPA essential • Pay attention to rigor • Be smart about scheduling • DAT/GRE/MCAT scores v. important • Take prep course if you can • Familiarity with computerized exams very useful • Get the books and use them • Internships invaluable • Do well, impress intern sponsors with work habits, curiosity, engagement • Letters of rec from professionals important • Choose extracurriculars wisely • Experiences which differentiate you from others should be pursued.

  5. Career Choices and Goals • Difference between stated goals in early career and path of career progression • Adjustments for academic reasons, for family reasons, for monetary reasons • Internships vital to assisting in career decisions • Solid academic preparation a must; later, pedigree important

  6. HAVE A PLAN • Map strategy for postgraduate plans • Engage in coursework, internships, research opportunities that mesh with goal • Make your postgraduate plans a reality – talk to representatives at schools to which you are applying, find out about schools, visit if possible • Senior year – backup plan in place BEFORE graduation

  7. The Secret Life of Vitamin AHolly Boettger-Tong, Wesleyan College Department of Biology

  8. What is Vitamin A ? • Required for normal vision reproduction,differentiation, homeostasis • Deficiency leads to blindness, sterility • Retinol, Retinal, Retinoic acid all have biological activity. • Nature of function depends upon form, converting enzymes, expression of receptors for each retinoid

  9. Retinoic Acid • Metabolite of Vitamin A • Organic compound that is produced endogenously and whose production is dependent upon tissue-specific expression of enzymes (retinaldehyde dehydrogenases, to be specific) • Affects vertebrate physiological processes • Development • Cell growth and differentiation • Morphogenesis • Adult tissue function

  10. Retinoid Isomer Structures All-trans Retinoic acid 9-cis Retinoic acid

  11. How Retinoic Acid Effects Gene Expression Retinoid binding protein Retinoic Acid Receptor – binds ligand and DNA, Influencing gene expression Gene product

  12. What is the Effect of Retinoic Acid During Early Development? • What are the dose-response characteristics of retinoic acid’s effects on Oryzias latipes development? • What insight into the role of retinoic acid in cardiogenesis might be gleaned from these experiments? • What are the gene expression changes associated with retinoid-altered development • How does the stage of development effect sensitivity to retinoid effects?

  13. Retinoids and Development • Specification of primary antero-posterior axis, forming nervous system, establishing limbs • Control of gene expression – produced at specific developmental times to yield a gradient of retinoic acid • Defects in retinoic acid production or in receptor expression result in defective development. Excess retinoic acid is teratogenic, causing malformations which are informative as to retinoid action in specific tissues.

  14. The Japanese Killifish • Oryzias latipes are native to Japan, Taiwan, and southeastern Asia • Freshwater and common to rice paddies • Rapid development (ranges from 1-3 weeks) in a translucent egg makes them ideal for determining potential teratologic effects of chemicals of interest • Good for students due to ease of culture

  15. Experimental Design • Modified FETAX – treat embryos for three days with different concentrations of retinoid (or vehicle control), then discontinue use and observe effects of treatment • Monitor embryos daily, observing morphology • Determine effects on hatching

  16. Dose Dependent Inhibition of Medaka Hatching by ATRA and 9-cis RA % Failed Hatching Dose of Retinoid (mM)

  17. Embryonic Morphology on Experimental Day 6 Control ATRA 9-cis RA 10nM 100nM 1mM

  18. Cardiac MorphologyIs Dramatically Altered by 100nM ATRA Treatment 100nM ATRA Control

  19. Cardiac MorphologyIs Altered by 50nM ATRA Treatment 50nM ATRA Control

  20. Range of Cardiac Malformations

  21. What are the Genetic Consequences of Treating Neurula Embryos with Retinoic Acid? • To study global changes in gene expression patterns we use DNA microarrays • Large numbers of genes (from 5-10K) represented on small coated glass slides (chips) • Assess changes in gene expression patterns in normal vs treated embryos (work in progress)

  22. What are the Effects of Retinoic Acid on Uterine Function? • Estrogen is a potent regulator of uterine growth • In immature rats, all uterine cell types proliferate in response to estrogen treatment • What effect, if any, does retinoic acid have on estrogen-induced uterine cell proliferation? • Can these effects be reiterated in vitro, using cultured primary cells? • Is there a difference in response between primary cells and immortalized cells?

  23. All-trans Retinoic Acid Inhibits Estrogen Induced Uterine Myometrial and Stromal Cell Proliferation 1. Treat animals with 30mg/kg ATRA prior to estradiol ( E2 stimulates cell proliferation in OVX rats) 3. Inject 3H Thy 4. Remove uterus 24 hrs post E2 injection 5. Section uterus 6. Expose to emulsion 7. Develop slides

  24. Why Switch to Cell Culture Experiments? Advantages: Easier to work with than whole animals More manipulable, faster results Greater range of treatment concentrations Cheaper Can extend studies to humans (cultured human cells) Disadvantages: May not reiterate effect seen in vivo Non-physiological Primary cells have limited lifespan

  25. Effect of Retinoic Acid on Human Myometrial Cell Proliferation

  26. Retinoic Acid Alters Uterine Smooth Muscle Cell Morphology Control, Day 6 10-9 M ATRA, Day 6

  27. Do Retinoids Influence the Growth of Immortalized Human Uterine Cells?

  28. Dose-Dependent Effects of ATRA on Immortalized Myometrial Cell Survival 10-11M ATRA Control 10-9 M ATRA 10-7 M ATRA

  29. What Is the Mechanism of Differential Sensitivity to ATRA Between Primary Non-Pregnant Cells and Immortalized Pregnant Cells? • Death due to necrosis or apoptosis? • Irrespective of Method of Immortalization? • What gene expression changes occur in pregnant vs non-pregnant myometrial cells? • Do any of these gene changes increase sensitivity to retinoids?

  30. What Secrets Have These Experiments Revealed About Retinoids? • Role of retinoids in heart development poorly understood • Implications for cardiac malformations in higher vertebrates (including man); opportunity to dissect gene pathway leading to chambering • Retinoic acid inhibits smooth muscle cell proliferation in both normal and benign tumor cells (implications for pharmacologic treatment of leiomyomas?) • Deducing mechanism of action may reveal more information about growth control mechanisms in these cells (implications for deciphering events during pregnancy which lead to myometrial cell hyperplasia)

  31. Acknowledgements • Namita Mohanty (GH 2003, “Comparative Effects of All-trans and 9-cis Retinoic Acid on Medaka (Oryzias latipes) Development” BIOS 76(1), 2005. • Erin Rooney (Pirate 2005, “Effects of All-trans retinoic acid on Immortalized Human Myometrial Cells”) • Munroe Sisters • Tri-Beta Research Foundation • NSF MRI 0116189

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