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 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 Still some male-dominated areas (eg., engineering, math, chemistry) where improvements can be made at both entry and advanced levels

The 2009 Graduating Class of the Medical College of Georgia School of Dentistry Applications Received Class Academic Qualifications Applications received for the 2005 entering class:237 Overall grade point average: 3.44 Applications received from Georgia residents: 237 Science grade point average: 3.37 Number of applicants granted interviews:131 DAT Academic Average: 18.6 Class size:62 DAT Perceptual Test Average: 17.7 Ratio of Georgia resident applicants to enrollees:3.82 to 1

Number of Applicants Number Enrolled Women / Men Enrolled Average Age of Enrolled (Range) At large28011/0* Georgia /1725 (20-40) Delaware1022/023 (*) South Carolina /222 (20-24) West Virginia 2965/121 (21-23) Totals /2024 (20-40) UGA Vet School Stats

Average scores for accepted applicants GPA Cum. GPA Science Last 45hr GPA GRE V+Q Comb. GRE Anal. GRE Biology At large ******* Georgia Delaware South Carolina West Virginia Overall

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

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

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

The Secret Life of Vitamin A Holly Boettger-Tong, Wesleyan College Department of Biology

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

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 Development Cell growth and differentiation Cell growth and differentiation Morphogenesis Morphogenesis Adult tissue function Adult tissue function

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

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

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?

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.

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

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

Dose Dependent Inhibition of Medaka Hatching by ATRA and 9-cis RA Dose of Retinoid (  M) % Failed Hatching

Embryonic Morphology on Experimental Day 6 Control ATRA 9-cis RA 10nM 100nM 1  M

Cardiac Morphology Is Dramatically Altered by 100nM ATRA Treatment 100nM ATRA Control

Cardiac Morphology Is Altered by 50nM ATRA Treatment 50nM ATRA Control

Range of Cardiac Malformations

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)

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?

All-trans Retinoic Acid Inhibits Estrogen Induced Uterine Myometrial and Stromal Cell Proliferation 1. Treat animals with 30mg/kg ATRA prior to estradiol ( E 2 stimulates cell proliferation in OVX rats) 3. Inject 3 H Thy 4. Remove uterus 24 hrs post E 2 injection 5. Section uterus 6. Expose to emulsion 7. Develop slides

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

Effect of Retinoic Acid on Human Myometrial Cell Proliferation

Retinoic Acid Alters Uterine Smooth Muscle Cell Morphology Control, Day M ATRA, Day 6

Do Retinoids Influence the Growth of Immortalized Human Uterine Cells?

Control M ATRA M ATRA M ATRA Dose-Dependent Effects of ATRA on Immortalized Myometrial Cell Survival

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?

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)

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