The 2002 Lectures in Biology: Cell Signaling in Health and Disease

Molecular and Cell Signaling

On its way to becoming an organism a single cell makes neighbors, then communities (tissues) and societies (organs). All these progressive and cascaded transformations and differentiation's of a single genotype into a multitude of morphological and metabolic phenotypes is the result of, and depend on a myriad, of molecular and cellular "communications". The cells receive them from their immediate chemical microenvironment and from other cells nearby and afar. These communications comprise the perception of chemical and/or physical perturbations (anthropomorphically called signals) on or around these cells. And the cells respond to these signals with signals of their own (by binding the chemical signal, by production of new molecules, by changing their shape, etc). This signaling is a dynamic and continuous process and the well being of the organism is critically dependent on a delicate equilibrium of the "give and take" of such signals. Departure from that equilibrium brings various states of disharmony and disease.

Understanding the molecular and cellular basis of signaling is thus of paramount importance to all aspects of life. This year’s Onassis Lecture Series will address the phenomenon of signaling at different levels of complexity reflected in the wide expertise of the invited speakers.

Issues that will be addressed are:

  • What constitutes a “biologically meaningful signal” ? They come in all forms: Physical and chemical “spikes” and gradients from temperature and/or pH fluctuations to inorganic ions (e. g. Ca++) and complex organic molecules (e. g. hormones).
  • What is the first response to the appearance of a signal ? It can be a binding to a receptor molecule, most frequently first at the cell surface, but it can also be a re-arrangement of the organization of an essential “target” macromolecule (e.g.; the refolding and/or covalent modification of a protein).
  • What happens after the initial signal has been “registered” ? Many things can happen! Most cells receive simultaneously a multitude of signals and they respond with multiple reaction pathways. Remember, the cell is in a dynamic state of a delicate equilibrium. A single "push" from that equilibrium will lead to multiple and diverse attempts to adjust to a new equilibrium.
  • How signaling is “terminated” ? Going through transitions, finally the cell will arrive at that state of the “new equilibrium” that can either initiate new changes (cascaded action) or, rarely, be an end state. Such states are reached by several mechanisms (e.g., protein phosphorylation or glycosylation, production of a second message, sequestration of the messenger, oligomerization of effectors and/or targets, etc.).
  • How is signaling at the cell surface “wired” to the gene expression machinery ? If the signal is to change the type and or level of genes “active” in a cell, it must be transduced to the nucleus. Hormones and small “second messengers” initiate and sustain these events. What are the pathways and the ways of getting the job done?
  • How such events influence cell differentiation processes (e.g., neural development,) cell surface pattern recognition and cell-cell adhesion. Attempts will be made to present cases of diseases resulting from “failed signaling” and ways to correct some of such diseases (e. g., congenital disorders of glycosylation, etc.).

Ample time for discussions and “work-shop” sessions will be available for the students to further develop issues that emanated from the formal presentation; or new ideas that “sparked” in their minds under the influence of the ambience of Crete, its culture and its countryside.

Edmond Fischer
Prof. Em., University of Washington
Nobel Prize(1992) in Medicine

Ernesto Carafoli
Prof. Em., ETH Zurich and
Prof., University of Padua

Anastassios Economou
Assist. Prof., University of Crete/FORTH

Hudson Freeze
Prof., University of California San Diego
Director, Burnham Institute

E. N. Moudrianakis
Prof., Johns Hopkins University and
University of Athens

Vassilis Pachnis
Head, Molecular Neurobiology Division
The National Institute for Medical Research,London

Athanassios Papavassiliou
Prof., University of Patras
Jacques Pouyssegur Director, Institute of Signaling ,CNRS,Nice
Monday 8 July09:15 - 9:45 R e g i s t r a t i o n
 09:45 - 10:00Welcome speech
by E.N. Economou
  10:00 - 11:15 "Cell regulation by protein Phosphorylation : A Historical Overview" by Eddy Fischer
  11:15 - 11:30 B r e a k
  11:30 - 12:45 "Calcium Signaling : A Tale Without Ends" by Ernesto Carafoli
  12:45 - 13:00 B r e a k
  13:00 - 14:15 "Calcium Signaling : A Tale Without Ends " continued
Tuesday 9 July 09:30 - 10:45 "How Proteins Speak With One Another" by Eddy Fischer
  10:45 - 11:00 B r e a k
  11:00 - 12:15 "MAP Kinase Signaling - Fidelity and Spatio - Temporal Control" by Jacques Pouyssegur
  12:15 - 12:30 B r e a k
  12:30 - 13:45 "Molecular Bases of Angiogenesis - MAP kinase and Hypoxia Signaling" by Jacques Pouyssegur
Wednesday 10 July 09:30 - 10:45 "Protein Tyrosine Phosphatases: A Different World" by Eddy Fischer
  10:45 - 11:00 B r e a k
  11:00 - 12:15 "regulation of Gene Expression through Transcription Factor Phosphorylation" by Athanasios Papavassiliou
  12:15 - 12:30 B r e a k
  12:30 - 13:45 " regulation of Gene Expression through Transcription Factor Phosphorylation " continued
  20:00 "Basic Biomedical research at  the Dawn of a New Century " by Eddy Fischer
Thursday 11 July 09:30 - 10:45 "Protein Glycosylation and Human Disease" by Hudson Freeze
  10:45 - 11:00 B r e a k
  11:00 - 12:15 "Protein Glycosylation and Human Disease " continued
  12:15 - 12:30 B r e a k
  12:30 - 13:45 "Trafficking of Membrane and Secretory Proteins" by Tassos > Economou
  13:45 - 14:45 L u n c h  B r e a k
  14:45 - 16:00 "Trafficking of Membrane and Secretory Proteins" continued
Friday 12 July 09:30 - 10:45 "Cell signaling in the Developing Nervous System" by Vassilis Pachnis
  10:45 - 11:00 B r e a k
  11:00 - 12:15 "Cell signaling in the Developing Nervous System" continued
 12:15 - 12:30B r e a k
  12:30 - 13:45 "Summary of the Lectures-Suggestions" by Van Moudrianakis (+ Audience)