Academic Background

Caterina Strambio De Castillia grew up in Italy and received her Laurea in Biologia (equivalent to B.S./M.S.) from the University of Pavia in 1988. She obtained her Ph.D. (1992-1998) working with Gunter Blobel at The Rockefeller University, where she investigated the manner in which the nuclear pore complex interfaces with the cellular genome in yeast. She continued this work at the same institution in the laboratory of Mike Rout, initially as a postdoctoral fellow (1998-2002) and then as a Research Associate (2002-2006). She then moved to the IRB-Bellinzona and to the University of Geneva, Switzerland, where she was a staff Research Scientist (2006-2012) developing imaging and proteomics methods to study the mechanism by which HIV-1 interacts with the host defense mechanisms to gain access to the cell nucleus. Her work has been supported by the American Cancer Society, the European Union and the Swiss National Science Foundation. In 2012, Dr. Strambio De Castillia joined the Program in Molecular Medicine at the University of Massachusetts Medical School.

Dissecting the interplay between HIV-1 and human cells during viral entry

After HIV-1 fuses with a target cell membrane, the virion core is delivered into the cytosol of the infected cell. A DNA copy (cDNA) of the HIV-1 RNA genome is produced by the HIV-1 reverse transcriptase (RT) and the cDNA is ligated to host cell chromosomal DNA by HIV-1 integrase. Despite 30 years of research, detailed understanding of these essential early steps in HIV-1 replication remains elusive. Some of the open questions ask:

1. Does the virion core need to undergo an “uncoating” process to enable reverse transcription?

2. Is RT active in the cytoplasm or the nucleus?

3. Does the intracellular path followed by the virion core influence its ability to give rise to a productive infection?

4. How does HIV-1 reach the nucleus?

Up to this point, progress has been impeded by the fragile nature of HIV-1 replication intermediates and the low infectivity-to-particle ratio of virions, which makes it difficult if not impossible to meaningfully dissect different steps in the pathway by bulk biochemical means alone.

Tracking HIV-1 as it traverses living cells in real-time

The goal of the Strambio De Castillia laboratory is to remedy this lack of understanding by developing methods to label and track infectious HIV-1 as it traverses living cells in real-time. The aim is to identify thoserare particles that have successfully integrated into chromosomal DNA, retrace their intracellular path as they travel to reach the cellular genome and identify their intracellular interaction partners, in a time and space resolved manner. Such information will be invaluable for furthering our understanding of the initial steps in the HIV-1 life cycle and for the rational design of anti-HIV-1 drugs that target them.

Quantitative analysis of viral trajectories gives insight about viral-host interactions

Using dynamic imaging followed by rigorous computational analysis of viral particle trajectories, the complex interplay between HIV-1 and cellular components can be solved.  A major hurdle, has been the difficulty of keeping track of multiple moving viral particles with sufficient temporal and spatial resolution while at the same time probing multiple experimental contexts.

A three-pronged multidisciplinary approach

In order to meet this challenge, the Strambio De Castillia group is engaged in a multidisciplinary, collaborative effort aimed at developing integrated workflows that will provide the analysis, data management and visualization capabilities required to drive a more complete understanding of viral-host interactions in the context of living human tissues. The project articulates on three fronts:

1. Real-time recording of HIV-1 viral core movement in infected human cells.

2. Viral particle tracking and motion analysis.

3. Building a novel bio-image informatics framework, called OMEGA, to support the comprehensive examination of particle movement across multiple experimental models and conditions.

OMEGA project website

More information on the OMEGA project can be found following this link:

http://big.umassmed.edu/omegaweb/