MRes Bioengineering Research Project
Title of the project: Synthetic Biology of mechanosensors
Supervisor 1: Professor Rob Krams
Department: Bioengineering
Imperial College campus: South Kensington Campus
email: r.krams@imperial.ac.uk
Supervisor 2: Dr Armando E. Del Río Hernández
Department: Bioengineering
Imperial College campus: South Kensington Campus
email: a.del-rio-hernandez@imperial.ac.uk
Project Description: (up to 200 words): Mechanical stimuli in the cardiovascular system determine a
wide range of physiological and pathological events ranging from blood vessel growth, remodelling
to atherosclerosis. Endothelial cells in the inner layers of these vessels are responsible to sense and
process these signals. We propose to combine synthetic biology techniques to monitor the activity
of mechanosensor molecules in the membrane of endothelial cells with magnetic tweezers, a
biophysical tool that allows the mechanical manipulation of biological entities. The activity of the
sensor will be monitored by a synthetic network, which activates a GFP molecule triggered by the
activation of a receptor in the membrane of the endothelial cell. The mechano-sensor will be
activated by two means: (i) using a coated bead, which will be coupled to the sensor and pulled by a
magnetic field; and (2) using home-made flow chambers to activate the endothelial cells in a flow
field. In this project, we are blending Synthetic Biology with Biophysical and Nanotechnological tools
crystallizing the experience of two group leaders in their fields.
Key techniques: Plasmid construction, transfection of genes in primary cells, cloning, sub-cloning,
flow experiments, magnetic tweezers and related biophysical tools.
References: (up to 3 references related to the project)
del Rio, A.; Perez-Jimenez, R.; Ruchuan, L.; R; Roca-Cusachs, P.; Fernandez, J. M. and Sheetz, M.P.
(2009) Stretching Single Talin Rod Molecules Activates Vinculin Binding. Science, 323, 638-641.
Roca-Cusachs P, del Rio A, Puklin-Faucher E, Gauthier NC, Biais N, Sheetz MP (2013) Integrindependent force transmission to the extracellular matrix by alpha-actinin triggers adhesion
maturation. PNAS, 110(15):E1361-E1370