Inflammation plays an important role in the development and progression of cardiovascular diseases. The modulation of inflammation and immunity by CD4+ regulatory T-cells has therefore received increasing attention. [1] The advent of advanced and single-molecule sensitive fluorescence microscopy methods now enables quantitative assessment of involved protein complexes and their interaction kinetics to further improve existing models of cell signalling. [2] In this context, we seek to establish robust methods for counting copy numbers of proteins participating in T-cell signalling using single-molecule fluorescence spectroscopy. [3] Important questions involve a comparison of the opportunities and limitations of existing methods (bleach-step analysis, cluster analysis, and photon-statistics based approaches) as well as the development of robust analytical tools. Here, we also plan to explore the potentials of machine learning for single-molecule data analysis. 

Applications are invited for a 3-year PhD fellowship funded by COMPARE (The Centre of Membrane Proteins and Receptors) in the laboratory of Prof. Dirk-Peter Herten. The appointed student will utilise different analytical tools, like machine learning, in combination with single-molecule fluorescence microscopy to compare existing methods, like bleach-step analysis, super-resolution cluster analysis and counting on photon-statistics (CoPS). Initially, the studies will focus on the theoretical exploration of methods aiming at analytical tools to investigate single-molecule data from in vitro and live-cell experiments. 

Supervisors; Professor Dirk-Peter Herten and Dr I Styles

Further details and application information can be found here

Inflammation plays an important role in the development and progression of cardiovascular diseases. The modulation of inflammation and immunity by CD4+ regulatory T-cells has therefore received increasing attention. [1] The advent of advanced and single-molecule sensitive fluorescence microscopy methods now enables quantitative assessment of involved protein complexes and their interaction kinetics to further improve existing models of cell signalling. [2] In this context, we seek to establish robust methods for counting copy numbers of proteins participating in T-cell signalling using single-molecule fluorescence spectroscopy. [3] We will establish the extent to which existing single-molecule methods, like Counting on Photon Statistics (CoPS), are capable of assessing dynamic changes in protein complexes (time-scales, sensitivity, etc.). 

Applications are invited for a 3-year PhD fellowship funded by COMPARE (The Centre of Membrane Proteins and Receptors) in the laboratory of Prof Dirk-Peter Herten. The appointed student will utilize tools from single-molecule fluorescence microscopy to study the molecular dynamics of bio-molecular complexes. Starting with a simple in vitro model as standard probe (hybridization of fluorescently tagged DNA oligonucleotides to an immobilized DNA) the studies will focus on investigating the required experimental conditions and the achievable time-scales to measure association and dissociation kinetics. Once established the studies will turn to experiments in vitro on immobilized protein complexes and, ultimately, to membrane associated protein complexes in live-cell experiments. 

Supervisors: Professor Dirk-Peter Herten and Dr Rob Neely

Further details and application information can be found here