Our research aims at improving the understanding of biochemical and transportation kinetics of signaling molecules that are controlling the gene expression in the cell.
Even the simplest organisms, viruses and phages, are perform- ing computations of input signals that are mediated trough networked molecular systems. At the molecular level, such networks arise from the collective system of molecules that chemically and physically interact with one another.The low- est level of processing is manifested by interactions between molecules, primarily proteins, and the DNA – the blueprint of the cell.
These computational molecular circuits display differ- ent dynamical behavior depending on the type of interaction and of the wiring of the network; stable steady states, bi- and multi-stability and oscillations. Examples of the latter are very common in all biological organisms and include e.g. cell division and circadian rhythms.
In E. coli the most known example of multi-stability is a molecular switch regulating the expression of the lac operon, a sequence of three genes coding for proteins used in the metabolism of lactose.The switch can be seen as a logical circuit on the transcriptional level, leading to efficient utilization of present energy resources.
The understanding of intracellular signaling is advancing rapidly on many levels. For many of the signaling networks however, little is known about the dynamics and the time scales of the signaling processes that the networks describe. For higher organisms like plants and humans such knowledge may give us the possibility of tuning or controlling specific processes.
For plants it may contribute to utilize energy more efficient in applications of biomass produc- tion and in for us humans it may imply that we can find more effective targets of drugs in medical applications.
Photosynthetic cells have genetic information encoded in both the nucleus and in the chloroplasts and (at least) two different machineries are responsible the protein synthesis of the chloro- plast genome.A nuclear encoded, eukaryotic, polymerase NEP is believed to encode the housekeeping genes of the chloroplasts and a plastid encoded, eubacterial-like, polymerase PEP that transcribes the photosynthesis related genes.
It is an ideal system for studying kinetic aspects of gene regulation since the temporal variations in the different reg- ulatory processes spans many orders of magnitude due to the separation of the regulatory signals between the chloroplasts and the nucleus.
The transport process of signalling molecules between the nucleus and the organelle imply that many aspects of the regu- lation are delayed. Information of the kinetics of the signalling network between the nucleus and the chloroplast is therefore necessary for understanding how e.g.the period of the circadian rhythm is related to the time scale of transporting molecules, i.e. the delay, between the organelle and the nucleus.
- A Grönlund, P Lötstedt, J Elf. Transcription factor binding kinetics constrain noise suppression via negative feedback.
- Nature Communications 4,1864 (2013).
- A Grönlund, P Lötstedt, J Elf. (2011). Delay-induced anomalous fluctuations in intracellular regulation. Nature Communications 2, 419 (2011)
- A Grönlund, P Lötstedt, J Elf. (2010). Costs and constraints from time-delayed feedback in small gene regulatory motifs. Proceedings of the National Academy of Sciences 107 (18), 8171.
- A Grönlund, RP Bhalerao, J Karlsson. (2009). Modular gene expression in Poplar: a multilayer network approach. New Phytologist 181 (2), 315-322.
- A Grönlund (2004). Networking genetic regulation and neural computation: Directed network topology and its effect on the dynamics.Phys. Rev. E 70, 06190