The Transcription Factor Titration Effect
Event details
| Date | 02.02.2017 |
| Hour | 14:00 › 15:00 |
| Speaker | Dr. Franz Weinert, California Institute of Technology |
| Location | |
| Category | Conferences - Seminars |
Abstract:
Developing a quantitative understanding of gene regulation challenges our knowledge of the underlying molecular processes. Additionally, it provides a framework for the creation of synthetic genetic circuits where, much like in the case of electronic circuits, the output can be predicted from the design. To my way of thinking, only when the designs are based upon predictive understanding will the field of synthetic biology really be able to deliver on its potential.
Previous models of gene regulation are often built around a picture of regulatory proteins called transcription factors acting on a single copy of their target gene. This idealization however, ignores the fact that transcription factors often regulate multiple genes, e.g. multiple identical copies of the target gene as well as additional genes that are regulated by the same transcription factors.
In my talk, I will present a phenomenon we have termed the transcription factor titration effect. The key point is that when the number of transcription factors is comparable to the number of copies of the gene controlled by that transcription factor, there are very strong (100-fold) effects on the resulting level of gene expression. In fact, the mere presence of unaffiliated, specific transcription factor binding sites leads to an identical result.
Using a thermodynamic model, we have very precise predictions for this effect and I will present a diverse collection of tests of these ideas using video microscopy of live bacteria by varying the number of gene copies on both chromosomes and plasmids, as well as by putting transcription factor binding sites in our cells on “competitor plasmids” that simply deplete available transcription factors. The predictions we make about the behavior of these regulatory situations are parameter free and yet, are in impressively good agreement with what we observe experimentally.
Developing a quantitative understanding of gene regulation challenges our knowledge of the underlying molecular processes. Additionally, it provides a framework for the creation of synthetic genetic circuits where, much like in the case of electronic circuits, the output can be predicted from the design. To my way of thinking, only when the designs are based upon predictive understanding will the field of synthetic biology really be able to deliver on its potential.
Previous models of gene regulation are often built around a picture of regulatory proteins called transcription factors acting on a single copy of their target gene. This idealization however, ignores the fact that transcription factors often regulate multiple genes, e.g. multiple identical copies of the target gene as well as additional genes that are regulated by the same transcription factors.
In my talk, I will present a phenomenon we have termed the transcription factor titration effect. The key point is that when the number of transcription factors is comparable to the number of copies of the gene controlled by that transcription factor, there are very strong (100-fold) effects on the resulting level of gene expression. In fact, the mere presence of unaffiliated, specific transcription factor binding sites leads to an identical result.
Using a thermodynamic model, we have very precise predictions for this effect and I will present a diverse collection of tests of these ideas using video microscopy of live bacteria by varying the number of gene copies on both chromosomes and plasmids, as well as by putting transcription factor binding sites in our cells on “competitor plasmids” that simply deplete available transcription factors. The predictions we make about the behavior of these regulatory situations are parameter free and yet, are in impressively good agreement with what we observe experimentally.
Practical information
- Expert
- Free
- This event is internal
Organizer
- Prof. Benoit Deveaud, Institute of Physics
Contact
- Blandine Jérôme