Visitors

During the visit we made significant progress on a project comparing the effects of transcriptional regulation with translation, proteolytic and allosteric regulation. This is based on a synthetic transcription factor constructed in the Semsey lab in Copenhagen, based on the Lac repressor of E. coli, that could be controlled simultaneously by all four types of regulators. Models developed by Sandeep Krishna during this visit enabled us to explore and compare the full range of dynamical capabilities of each regulatory mechanism. A paper on this has been submitted to the Journal of Biological Chemistry. In addition, the visit triggered a new collaboration between with Aswin Seshasayee (NCBS) studying restriction-modification systems (RM-systems) in bacteria, which are thought to be important defense mechanisms against bacteriophage attack. Our preliminary simulations suggest that weak RM-systems are not particularly useful as defenses against phage, but are extremely important for creating phage that can be used by one bacterial strain as a weapon against other competing strains. A manuscript on this work is under preparation.

This visit was instrumental in the completion of an existing project, studying protein roadblocking of DNA transcription in bacteria. Genomic DNA is bound by many proteins that could potentially impede elongation of RNA polymerase (RNAP), but the factors determining the magnitude of transcriptional roadblocking in vivo are poorly understood. We have been combining systematic experiments (in Ian Dodd’s laboratory) and mathematical modelling (a collaboration between Kim Sneppen and Sandeep Krishna) to analyse how roadblocking by the lac repressor (LacI) in E. coli cells is affected by promoter firing rate, the concentration and affinity of the roadblocker protein, the transcription-coupled repair protein Mfd, and promoter-roadblock spacing. In this visit we were able to build models of RNAP traffic and LacI roadblocking, and combine them with experiments to make specific predictions that will lead to further experiments. In the spring of 2014 we submitted a manuscript on this work to Nucelic Acids Research where it is currently under second round of reviewing after revisions.

Shreyas Mandre and Madhu Venkadesan are co-investigators on a project funded by the Human Frontier Science Program to study the biomechanical function and evolution of the human foot. As part of this project, we are working on problems ranging from measurement of elasticity of the foot from human subject experiments to understanding the limits of foot function by extending MV’s work on optimal control to spatially extended elastic bodies such as the foot. Shreyas Mandre also has overlapping research interests with Madan Rao. Following Shreyas' recent work on the near field capillary attraction between objects of different shapes floating on a fluid surface, Madan has been iscussing how local deformations of the fluid membrane can induce attraction between two proteins or protein aggregates of different shapes. Madan Rao's group has been working on phase segregation and dynamics of clustering of molecules induced by active stresses and currents. One way to approach this problem is via boundary layer theory. They have been discussing many aspects of this problem with Shreyas Mandre. Madan and Shreyas share a common interest in the mechanics of solids and fluids at low Reynolds numbers, and its fascinating applications to problems of biological interest. As a result of Prof. Mandre's visit to NCBS, we have submitted two conference abstracts, and are in the process of working on at least two collaborative journal articles.

This visit was an extension of a long-standing collaboration on various aspects of oscillatory behaviour in biological systems. Recently we have been studying entrainment and synchronization in
coupled oscillators involved in vertebrate somitogenesis. During the visit we initiated a new collaboration with Sanjay Sane (NCBS) on coupled oscillators in insect wings. Our plan is to formulate a model based on Lagrangian dynamics in order to describe the coupling between the large wings on the insect and the smaller wings on the back, called halteres. Halteres are thought to be
important in stabilizing flight, but their precise role in this is not understood. We are interested in the synchronization between the two oscillating system under change of the frequency of the larger wings, obtained by cutting the length of the wings. We have recently obtained funding from The Danish Research Council for a PhD working on this project.