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Systems Microscopy

Project Leader: Dr Alessandro Esposito

 

Our major focus is to develop new methods for probing and mapping the biochemical events that underlie cellular systems using fluorescence microscopy, with the overall aim of better understanding the fundamental principles that govern tumour suppressive mechanisms and their perturbation in cancer.

Many forms of cancer begin with oncogenic events, which, in normal cells, elicit growth cessation or cell death rather than transformation, due to the activation of tumour suppressive networks. We are interested in dissecting the signaling pathways that lead from oncogenic events to tumour suppressive mechanisms, and in particular, how cells integrate extracellular and intracellular signals to preserve tissue-, cell- and genome homeostasis in the face of oncogenic challenge.

Probing cellular function and tissue architecture using new methods in imaging.  

 

Our research spans these broad areas:

  • Development of new microscopy platforms: New technologies that can achieve the highest spatio-temporal resolution of cellular signaling to decode complex networks of molecular interactions (e.g., hyper-dimensional imaging microscopy).
  • Biological sensors: New FRET pairs and FRET sensors to probe the signaling pathways activated in response to oncogenic stimuli that elicit tumour suppressive responses.
  • Biophysics and modeling: Models for biochemical pathways and mathematical tools to decode the complex information acquired with the new generation of microscopes.

We are also committed to transfer technologies and knowledge to translational research activities both in the areas of drug discovery (with the Chemical Biology & Molecular Therapeutics Initiative and the Cambridge Molecular Therapeutics Programme) and tumour imaging for diagnostic application (with clinical collaborators at the Addenbrooke’s Hospital). 

 

Selected Publications:

Fast and simple spectral FLIM for biochemical and medical imaging. Popleteeva M, Haas KT, Stoppa D, Pancheri L, Gasparini L, Kaminski CF, Cassidy LD, Venkitaraman AR, Eposito A. Opt Express. 2015 Sept 7; 23 (18):23511-25. PMID: 26368450

Maximizing the biochemical resolving power of fluorescence microscopy. Esposito A, Popleteeva M, Venkitaraman AR. (2013) PLoS One. 2013 Oct 28;8(10):e77392. doi: 10.1371/journal.pone.0077392.

Design and application of a confocal microscope for spectrally resolved anisotropy imaging. Esposito A, Bader AN, Schlachter SC, van den Heuvel DJ, Schierle GS, Venkitaraman AR, Kaminski CF, Gerritsen HC. Opt Express. 2011 Jan 31;19(3):2546-55. doi: 10.1364/OE.19.002546.

Continuous polo-like kinase 1 activity regulates diffusion to maintain centrosome self-organization during mitosis. Mahen R, Jeyasekharan AD, Barry NP, Venkitaraman AR. Proc Natl Acad Sci USA. 2011 May 31;108(22):9310-5.

DNA damage regulates the mobility of Brca2 within the nucleoplasm of living cells. Jeyasekharan AD, Ayoub N, Mahen R, Ries J, Esposito A, Rajendra E, Hattori H, Kulkarni RP, Venkitaraman AR. Proc Natl Acad Sci USA. 2010 Dec 14;107(50):21937-42.