Workpackages

WP1 - WP Leader: Partner 3

CELL SYSTEMS FOR SCREENING AND ASSESSMENT OF TISSUE-SPECIFIC ACTIVITIES OF COMPOUNDS ACTIVE THROUGH ERs

Objectives
- set up growth conditions of cell systems representative of reproductive and non reproductive tissues
- identification of genes "signature" of the activity of estradiol and synthetic estrogens in specific target tissues
- verify how ER isoforms mediate the activity of estrogenic compounds in reproductive and non reproductive organs

WP2 - WP Leader: Partner 3

INNOVATIVE ANIMAL MODELS FOR THE ASSESSMENT OF ESTROGEN RECEPTOR ACTIVITY

Objectives
- to provide novel mouse models for the rapid, innovative screening of compounds active on ERs based on in vivo imaging technologies
- to provide models to functionally dissect and characterize the molecular mechanisms that underlie the numerous physiological effects mediated by estrogen and/or their nuclear receptors.
- to provide models that allow for a global view of ER activity in aging female animals.

WP3 - WP Leader: Partner 1

IN VIVO PROFILING OF THE ACTIVITY OF COMPOUNDS ACTIVE THROUGH THE ERs

Objectives
- to set up protocols to compare modalities of hormone replacement therapy in vivo
- to verify the physiological significance of unliganded activation of ER in non-reproductive organs and the possibility of generate modalities of unliganded activation of ER which mimic the physiological status.

WP4 - WP Leader: Partner 4

ESTROGEN ACTION IN AGING BRAIN

Objectives
- to investigate on the neuroprotective and anti-inflammatory effects of estrogenic compounds in experimental models of degenerative and inflammatory diseases of the brain
- to assess whether aging and the duration of estrogen deprivation may affect the neuroprotective role of estrogens
- to investigate on the molecular mechanism of estrogen anti-inflammatory activity.

WP5 - WP Leader: Partner 6

AGING OF THE CARDIOVASCULAR SYSTEM AND DIABETES: ROLE OF ESTROGENS

Objectives
- to assess the metabolic features of the menopause and the impact of HRT on:
a) energy homeostasis and substrates oxidation;
b) insulin sensitivity with respect of glucose, fatty acids and amino acids metabolism;
c) body composition and ectopic fat accumulation (within the skeletal muscle and the liver);
d) lipid profile and markers of low-grade inflammation;
e) plasma adipokines (leptin, adiponectin, resistin);
- to assess the effect of menopause and of replacement estrogen-therapy are the major markers cardiovascular risk factor.

WP6 - WP Leader: Partner 2

ESTROGENS AND INFLAMMATORY DISORDERS LINKED TO FEMALE AGING


Objectives
- to investigate the effects of estrogens on inflammatory disorders linked to aging, specifically the local tissue repair process.
- to determine the dose-dependent effects of estradiol, SERMS and phytoestrogens on the local inflammatory response using well-characterized in vivo animal models of tissue injury and repair;
- to investigate the role of progestins, and their interaction with estrogens, on the in vivo inflammatory and tissue repair responses;
- to investigate the specific effects of estrogenic/progestin compounds on the responses of isolated inflammatory cells (neutrophils and monocyte/macrophages).

WP7 - WP Leader: Partner 1

DISSEMINATION AND EXPLOITATION


Objectives
- to disseminate the project results;
- to reach all the potential audience, in particular: patients' organizations, scientific societies, public health authorities, biotechnological and pharmaceutical companies, etc.;
- to exploit project results

WP8 - WP Leader: Partner 1

MANAGEMENT AND QUALITY ASSURANCE


Objectives
- To define the detailed implementation plan;
- To coordinate the project components;
- To assure a timely reporting of the project to the EC,
- To establish and adopt common operational procedures
- To check progression of the project activities, ensuring adherence to project timetable, implementing corrective actions, if any, and preventing possible delays or unsuccessful results;
- To ensure respect of ethical issues and attention paid to gender issues;
- To ensure a high qualitative level of scientific and technical results;
- To ensure a correct financial management and reporting.