The Nation's Investment in Cancer Research

Following Important Leads

Subcellular Imaging

Residing inside the cell’s nucleus, the genome is, we have discovered, highly organized. The positions of many genes and genomic regions change during physiological processes, and those changes may provide the earliest foreshadowing of cancer development.

That remarkable knowledge comes from imaging that has moved far beyond the realm of the diagnostic. Advances in imaging devices and contrast agents used to improve image quality are revolutionizing how cancer researchers look inside cells and, consequently, think about cancer diagnosis and treatment.

“We’re at a point where we now understand the fundamental concepts, the fundamental principles by which genomes are organized in the nucleus, and I would argue, even the principles by which genomes function,” said Thomas Misteli, Ph.D., the head of NCI’s Cell Biology of Genomes group in the Center for Cancer Research. The next step, said Dr. Misteli, “is to link some of these morphological observations to function, to physiology, and to disease.”

Technological breakthroughs combined with advances in computational analysis of imaging data have driven the field dramatically forward. It has now become possible to visualize nuclear processes and movement of gene loci in single living cells, and generate spatial maps of how genomes are organized in the nucleus.

“This is an area of research that five or six years ago, literally nobody in the United States worked on because it was extremely high risk,” explained Dr. Misteli. “I came to NCI because it provided a lot of freedom to do high-risk research, which is increasingly more difficult in the outside [research] world.”

Sriram Subramaniam, Ph.D., of the Laboratory of Cell Biology in NCI’s Center for Cancer Research, recently published research using electron tomography to visualize the way HIV enters and infects cells. “We can enter structures in their native, physiological context and essentially… zoom into cells, increasing the magnification to a point where you can actually see the atoms and molecules,” said Dr. Subramaniam. “Although you cannot do this with a single microscope, the combination of things we are doing experimentally and computationally has the end effect that we are literally walking into these viruses and cells at resolutions that are close to looking at these structures and molecules directly.”

“Previous research showing how HIV interacts with immune system cells and antibodies has been important in vaccine design,” said Dr. Subramaniam. “However, understanding the complete structure of the viral spike may reveal other vulnerable targets. This knowledge will be crucial to solving the puzzles associated with strategies at the heart of virus invasion.”