Cellular function is regulated by molecular spatial distributions, interactions, and dynamics, all of which are often perturbed during cancer progression and metastasis. To quantify molecular structures and the interplay between molecules requires accurate 3D imaging of single molecules at the nanoscale.

In this work I will fill three technological gaps and develop an innovative and versatile imaging platform for simultaneous multi-color 3D single-molecule super-resolution imaging and 3D chromosomal loci tracking with high spatiotemporal resolution throughout entire live cancer cells. I will then use my platform to deduce molecular mechanisms for improved understanding of cellular function, ...

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Cellular function is regulated by molecular spatial distributions, interactions, and dynamics, all of which are often perturbed during cancer progression and metastasis. To quantify molecular structures and the interplay between molecules requires accurate 3D imaging of single molecules at the nanoscale.

In this work I will fill three technological gaps and develop an innovative and versatile imaging platform for simultaneous multi-color 3D single-molecule super-resolution imaging and 3D chromosomal loci tracking with high spatiotemporal resolution throughout entire live cancer cells. I will then use my platform to deduce molecular mechanisms for improved understanding of cellular function, pathogenesis, and treatment of cancer.

Aim 1: Tracking of multiple chromosomal loci in 3D throughout live cancer cell nuclei. I will develop an imaging platform that will allow direct mapping of the precise 3D chromatin dynamics in different cancers, and I will show how telomere dynamics and organization are linked to cancer progression and tumorigenesis.

Aim 2: Molecular distributions and interactions in 3D throughout cancer cells. My proposed work will extend my imaging platform to enable direct correlation between the 3D morphology of nanoscale cellular structures and I will show how such structures and molecular distributions are affected in various cancers and during cancer progression and metastasis.

Aim 3: Correlative 3D chromatin dynamics and protein distributions throughout live cancer cells. The imaging platform resulting from this aim will allow for correlative live-cell 3D chromosomal loci tracking and 3D single-molecule super-resolution imaging throughout live cancer cells. I will use my platform to directly map the correlation between telomere size and dynamics in individual cancer cells at various telomerase levels.

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