Toward Problem-Solving Models of Gene Expression Regulation
Introduction
In 2001, in my class on Information Technology in Biology Education, we challenged students to propose a design for a problem-solving environment in "gene expression". One student, Mary Mawn, proposed a design based around the lac operon, but didn't see how it could be built. For a couple of years, I had the idea that such a thing would be possible to build in Netlogo, but didn't have the incentive to sit down and write the code. In 2004, a group of us at the BioQUEST curriculum consortium talked about the need for materials to support learning in this area and, during summer workshop, created a set of three models using netlogo to illustrate regulation of gene expression. The first model was of a classic system: the lac operon and allowed students to simulate the behavior of wildtype bacteria and of lacZ and lacI mutants in the presence of an inducer. The second model was inspired by a presenter who showed how signal transduction pathways can act as logical gates. In the second simulation, pairs of genes influence the expression of a third gene. The third model presents a set of unknown problems to students and challenges them to document the interactions among 5 genes. The goal of this paper is to document what we've learned in using these models in pilot testing and in our full laboratory sequence and to outline an agenda toward capturing the full range of complexity in problem-solving in the regulation of gene expression.
Lac Operon
The lac operon was the first model of how gene expression was regulated (Jacob & Monad, 1961) and is frequently presented in textbooks.
even simple problems confusing to novices
Logical Promoter
students discover need to use a systematic approach
leakiness of gates
Unknown
three possible outcomes: oscillation, fixation, stochastic outcome (due to a race condition) with internal or external initiation.
Currently Modelled Phenomena
transcription factor binding, transcription, repression of transcription, translation, combinatorial promoter interactions
Additional Phenomena Needed
Signal Transduction
RNA Processing
alternate splicing
Product Complexity
dimerization, allosteric regulation of enzymatic activity
Large-scale Patterns of Expression
simulations of microchips
References
Jacob F; Monod J (June 1961). "Genetic regulatory mechanisms in the synthesis of proteins". J Mol Biol. 3: 318-56.