Scialog: Collaborative Teams - 2015
Physics, Boston University
Rethinking the Idea of Cell Type
The cells in a living organism such as a mouse or a human can be highly specialized. But precisely how cells become specialized is an open question for researchers.
Recently two of those researchers have begun collaborating to challenge the traditional view of cell specialization. Grégoire Altan-Bonnet, head of the ImmunoDynamics group at New York City’s Sloan-Kettering Institute, and Pankaj Mehta, a theoretical biophysicist at Boston University, hope to test the startling hypothesis that even cells which appear to have settled irreversibly into specialized roles within the body can, under certain circumstances, spontaneously transition in vivo to new roles in a process the researchers have termed “phenotypic tunneling.”
“Phenotype” refers to the observable properties of an organism produced by the interaction of its genetic makeup and the environment. “Tunneling” here is used in analogy to a term in quantum physics that refers to a subatomic particle, such as an electron, moving through a barrier that classical physics says it shouldn’t be able to penetrate.
In testing their theory, Altan-Bonnet and Mehta will be employing cutting-edge research procedures they have already developed.
Basically the plan calls for injecting hematopoietic stem cells – the blood cells from which all other blood cells arise – taken from one specially bred mouse into a target mouse of a slightly different genetic makeup. The two mice are essentially identical except for certain very specific genes. Then, at specific intervals, blood, lymph tissue or bone marrow samples will be taken from the target mouse and analyzed for cellular changes reflecting the first mouse’s unique genetic markers.
The analysis involves the use of mass cytometry, an exquisitely sensitive form of mass spectrometry in which antibodies in the cells are tagged with rare earth elements and the cells are then broken down and sent into a plasma jet. The wavelengths of light given off by the burning material can reveal more than 40 different qualities in the cells, including, the researchers hope, genetic mutations in the target mouse caused by the cells from the first mouse.
In order to understand the experimental data, the researchers will use a theoretical framework for combining ideas from physics with large genomic datasets to construct “epigenetic landscapes” that they hope will yield new insights into the molecular basis of cellular reprogramming.