the specific environmental stress of iron limitation. The essential nutrient iron lies at the competitive interface between the mammalian host and nearly all microbial pathogens, including Hc. The host displays both constitutive and inducible iron sequestration mechanisms. Iron limitation acts as an important host defense mechanism against Hc in human and mouse macrophage cell culture infection models. As a successful pathogen, Hc must express iron acquisition mechanisms to obtain this nutrient in the competitive host environment in which it resides during infection. Hc previously has been shown to produce hydroxamate siderophores, which typically act as iron-scavenging compounds. We have demonstrated ferric reduction by Hc via at least three moieties—an extracellular ferric reductase enzyme, extracellular ferric reductant(s), and cell-surface ferric reducing agent(s). Reduction of ferric to ferrous iron causes removal from both host (e.g., transferrin) and fungal (siderophore) iron-binding compounds. Siderophore-mediated and reductive processes may provide important alternate, complementary, or interactive mechanisms for acquiring iron in the soil and/or the host.

George D. Yancopoulos M.D., Ph.D.

President, Regeneron Laboratories

Chief Scientific Officer, Regeneron Pharmaceuticals, Inc.

Growth factor and cytokines, released by one cell and acting via cell surface receptors on a second cell, mediate intercellular communications required for the initiation and/or regulation of all biologic processes. A major focus for us at Regeneron has been to identify new growth factors and/or their receptor systems, with the notion that identification of such critical master regulatory systems would present new therapeutic opportunities. We have particularly focused on growth factor/receptor systems that specifically act on a single or limited number of cell types, so that manipulation of these systems could be attempted so as to benefit diseases involving those cell types, without having widespread side effects. Over the last decade, our efforts have led to the discovery and characterization of multiple growth factor/receptor systems (e.g., neurotrophins and their Trk receptors; CNTF/IL6 family and their gp130-related receptors; agrin and its MuSK receptor; collagens and their DDR receptors; ephrins and their Eph receptors; angiopoietins and their Tie receptors;

Front Matter (R1-R10)

Selected Invited Conference Papers1 Markey Scholars Update (1-6)

2 Ensuring the Future Participation of Women in Science, Mathematics, and Engineering (7-12)

3 The Future of Non-profit Funding in Biomedical Research (13-23)

4 New Directions in Genomic Research (24-28)

Papers Presented by Markey Scholars5 Functional Genomics (29-41)

6 Electrophysiology of Synapses (42-49)

7 Transcription, Chromatin Assembly, and Homologous Recombination in Chromatin (50-72)

8 The New Biology (73-79)

9 Signal Transduction in Bacteria (80-89)

10 AAK1, A Novel Kinase That Regulates Cargo Selection for Clatherin-Mediated Endocytosis (90-96)

11 Abstracts of Poster Sessions (97-152)

Appendix A: Conference Agenda (153-157)

Appendix B: Speakers Biographical Sketches (158-161)

Appendix C: Conference Participants (162-166)