Upload
roger961
View
168
Download
1
Tags:
Embed Size (px)
Citation preview
Molecular genetic pathway of human sex determination Vince HarleyVince Harley
Embryonic gonad at 6 weeks & 7 weeks gestation
SRYtestis
ovary
SOX9
XY
XX
Swyer Syndrome ….Campomelic Dysplasia ….
What genes do SRY and SOX9 turn on and how?
Are SRY/SOX9 target genes intersex genes?
What is the molecular effect of clinical SRY/SOX9 mutations?
QUESTIONS:
Molecular biology, cell biology, protein biochemistry
human intersex patients, human EC lines, mouse knockouts,
TECHNIQUES& reagents
Female Reproductive Endocrinology Group: Prof. Jock Findlay, Dr Ann Drummond, Dr Paul Farnworth
Progesterone receptors
Androgen
PrimaryPrimordial
Secondary
Preovulatory
Corpus luteum
LH receptorsGranulosa cell
Atresia
Developing Follicles
Ovulation
Theca (androgens)
Oocyte
(progesteroneestrogen)
AndrogenOestrogenFSH receptors
The hormonal regulation of sperm production: David Robertson, Dr Peter Stanton, Dr Sarah Meachem, Prof Rob MacLaclan
Why are we interested?
• to understand the process of sperm production (spermatogenesis) in the healthy male
• to apply this knowledge to the development of treatments for male infertility
• to devise effective and reversible hormonal contraceptives for men
E2
Techniques• cell culture• transfection• RNA analysis• DNA / protein interaction
Breast cancer and estrogens: Prof Evan Simpson, Dr Colin Clyne
•Male reproductive system
•Dietary studies
•Adiposity
•Female reproductive system
The Aromatase knockout (ArKO) mouse
•Brain
Prof Evan Simpson, Dr Margaret Jones
Endocrine Cell Biology: Endocrine Cell Biology: Dr Chen ChenDr Chen Chen
• Type-II diabetesType-II diabetes – approx. 1 million Australians – approx. 1 million Australians – influence of adipocyte-derived factors on pancreatic influence of adipocyte-derived factors on pancreatic
ββ-cells-cells
– co-culture b-cells with fat cellsco-culture b-cells with fat cells
• GH deficiency in GH deficiency in ageing populationageing population – pituitary somatotropes in ArKO micepituitary somatotropes in ArKO mice
• OObesitybesity and GH deficiency and GH deficiency – leptin-from fat, orexin-from CNS, and ghrelin-from leptin-from fat, orexin-from CNS, and ghrelin-from
stomachstomach..
Uterine Biology GroupUterine Biology Group
Mission:Mission: to improve women’s healthto improve women’s health by- by-
• Increasing contraceptive choices for womenIncreasing contraceptive choices for women
• Improving fertility of infertile womenImproving fertility of infertile women
• Reducing / treating uterine bleeding Reducing / treating uterine bleeding problems problems
NP
d3.5
Imp
Inte
r
Imp
Inte
rd4.5 d5.5
Prof Lois Salamonsen, Dr Eva Dimitriadis, Dr Guiying Nie, Dr Naomi Morrison
1. Granulosa Cell Tumours (GCT)1. Granulosa Cell Tumours (GCT)
• 5% of malignant ovarian tumours
•Approach: tumour bank and cell lines
Our focus has been on:• profiles of gene expression: candidates & microarray • signalling pathways – constitutive activation• expression of ERβ
•coregulatory molecules• ERβ-induced genes
• mutation detection
Prof Peter Fuller
2. Mineralocorticoid Receptor Structure-2. Mineralocorticoid Receptor Structure-Function ProjectsFunction Projects
• ligand binding specificityligand binding specificity
• interdomain interactions• coregulatory proteins
Prof Peter Fuller
HypertensionHypertensionHypertrophyHypertrophy
Vascular InflammationVascular InflammationCardiac FibrosisCardiac Fibrosis
AldosteroneAldosterone
↑↑ ExtracellularExtracellularPotassiumPotassium
Fluid andFluid andelectrolyte electrolyte homeostasishomeostasis
3. Mineralocorticoids and heart disease3. Mineralocorticoids and heart disease
MRMR
RAASRAAS
In 2002, CVD claimed the lives of 50,000 Australians (~40% of all deaths)
Heart failure accounts for many of these deaths
Prof Peter Fuller and Dr Morag Young
PRINCE HENRY’S INSTITUTEPRINCE HENRY’S INSTITUTESTUDENT OPEN DAYSTUDENT OPEN DAY
Come and meet our researchers Come and meet our researchers and take a tour and take a tour of our facilitiesof our facilities
Tuesday 8 AUGUST 2006Tuesday 8 AUGUST 200610am – 12pm10am – 12pmFriday 11 AUGUST 2006Friday 11 AUGUST 20061pm – 3pm1pm – 3pm
Prince Henry’s InstitutePrince Henry’s InstituteLevel 4Level 443 – 51 Kanooka Grove43 – 51 Kanooka GroveClayton VIC 3168Clayton VIC 3168
www.princehenrys.org
Experimental approachExperimental approacheses
• Molecular biologyMolecular biology: RT-PCR: RT-PCR, RNAi (reduced , RNAi (reduced expression) and transfection (over-expression)expression) and transfection (over-expression);;
• HistochemistryHistochemistry: receptor and ligand localisation;: receptor and ligand localisation;
• Patch clampPatch clamp: ion channel and electrophysiology;: ion channel and electrophysiology;
• [Ca[Ca 2+2+]] ii: microphotometric recording for real-time and : microphotometric recording for real-time and confocal microscope for spatial distribution;confocal microscope for spatial distribution;
• ExocytosisExocytosis:: single cell-fluorescent Zinc (Insulin), single cell-fluorescent Zinc (Insulin), capacitance, amperometry; population-RIAcapacitance, amperometry; population-RIA..