Future Challenges in Theoretical Biology

This will be a rather informal Work Group in the literal sense of the word. Thus there is no detailed schedule yet, this will be organized in the first session on Monday morning after breakfast.

Below is a list of discussion topics that have been contributed by the invited participants.

Theoretical Biology - Not even wrong?

A collection of questions addressing the relationship of Theoretical Biology and (minimal) mathematical models.

Regulation and Evolution of Regulation

• A wide variety of large scale experiments are currently accumulating

data which are supposed to enhance our understanding of gene regulation and the organization of regulatory regions. Nevertheless, the conclusions drawn from these data are mostly vague. Computational models for the prediction of regulatory regions and their regulatory function are usually based on assumptions drawn from a small number of well studied examples for which large scale studies commonly fail to prove generality. Regulatory networks, often uncoupled of time and space, are built but the nature of the links is largely unspecified. Synergistic effects are often suggested where actual context/interaction information is missing.

Are we still missing important facts or concepts of regulation to fully describe a genes expression pattern?

We already know about many levels or regulation. How complicated can it get? (regulatory catastrophe)

Which information do we really need to understand the mechanisms of gene regulation?

• Regulation is currently viewed as a process that follows a

genetically determined regulatory program which, once initialized with the same input, originates in the same output, e.g. phenotype of identical twins. This suggest a tight control coded somehow in the genome. Nevertheless, expression profiles, and temporal and spatial expression patters seem to vary considerably among individuals. Furthermore, major changes in the phylogeny are now frequently attributed to changes in regulatory regions and therefor gene expression patters and profiles.

How can tight control allow so much flexibility?

How do innovations arise from changes in regulatory regions?

• Most of the assumptions about the organization of regulatory

elements seem reasonable from an engineering point of view (only). Among those are, e.g., absence of "unnecessary" elements, modularity of regulatory regions, usage of comparable regulatory elements by co-expressed genes, organization of joined genes in gene batteries etc. Did evolution really structure regulatory regions in this way?

How do gene expression patters/profiles evolve?

How does gene regulation evolve?

What can we learn about gene regulation from the evolutionary history of the gene and it's regulatory region?

How would an appropriate evolutionary model for regulatory regions look like?

How can "old" genes follow new regulatory trends (emergence of CpG island promotesr, miRNAs, binding site turnover, etc.)?

How does a gene acquire a "second function" in terms of a new and additional spatial and temporal expression pattern?

Do we expect to see co-evolution of gene function and gene regulation?

The Gene Concept