Dr. Sriram Subramaniam and his team in CCR's Laboratory of Cell Biology develop tools and strategies for capturing images of cells and viruses, with a focus on HIV and cancer. His group recently won an award for the image of a melanoma cell (below) and published three-dimensional (3D) images of the structures HIV uses to enter cells, created with a technique called electron tomography.
What is your mission?
Our mission is to develop imaging technologies that can begin to zero in on cells and viruses at progressively higher resolutions. It seems like science fiction, but by using advanced imaging methods and computational tools, one can, in essence, walk into a cell and "see" the structures of specific molecules. This information is critical to understanding how cells are organized, and it also advances our efforts at NCI to discover what makes cancer cells different from normal cells and to design more effective vaccines strategies against HIV. Our technologies are especially powerful for addressing questions in structural biology that have not been tackled previously because the necessary tools did not exist.
What are your interests?
In the spectrum of imaging that runs from small molecules all the way up to humans, there are many gaps in what can be captured. We are most interested in the gap between molecules and cells, which includes structures such as retroviruses and mitochondria, the energy producers of cells. These structures carry out important work, yet they cannot be easily studied at molecular resolution by conventional imaging tools.
Have your melanoma studies revealed surprises?
Yes. These studies have provided fascinating glimpses of the interior of the cell. We have seen shapes that don't look anything like what you might expect based on textbook pictures from electron microscopic imaging of thin sections through these cells. We have also figured out how to translate these images into three dimensions and are developing automated tools to extract the wealth of structural information in these 3D cellular images.
How is this information relevant to patients?
Our technology allows you to mine the cell images for "markers" that may be related to the fate of the cell or the distribution of antigenic markers and drugs. For instance, we can quickly determine if there are changes in the proportion of the volume of a melanoma cell that is occupied by mitochondria and connect this information with biochemical findings. These are still early days, but this or a similar quantitative marker based on novel imaging tools may provide diagnostic or prognostic information on cancer. We are essentially charting new territory in documenting what happens within the cell.