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Researchers Team Up to Determine If Specialized Cells Can Switch Roles

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. 

Altan-Bonnet and Mehta are among 50 early career scientists participating in Scialog: Molecules Come to Life, a two-year program jointly sponsored by Research Corporation for Science Advancement (RCSA) and the Gordon and Betty Moore Foundation. Scialog supports research, intensive dialog and community building to address scientific challenges of global significance. Within each multi-year initiative, Scialog Fellows collaborate in high-risk discovery research on untested ideas and communicate their progress and form new collaborations in annual conferences.

Molecules Come to Life focuses on such questions as, what are the fundamental principles that make a collection of molecules within a cell produce behaviors that we associate with life? How do molecules combine and dynamically interact to form functional units in cells, and how do cells themselves interact to form more complex lifeforms?

The researchers formed their collaboration at a Scialog conference held earlier this year at Biosphere2 north of Tucson, Arizona. There scientists from divergent fields of biology, physics and chemistry engaged in intensive discussions designed to produce creative ideas for innovative research.

“Scialog aims to encourage collaborations between theorists and experimentalists,” said RCSA Program Director Richard Wiener. “And, we encourage approaches that are driven by theory and coarse-grained modeling, that are testable by experiments.”

The next Molecules Come to Life Scialog conference will be held in March 2016. 

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