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HSCI Science Update: August 2011

August 22, 2011

  • Getting Stronger All the Time: A Future for Spinal Muscular Atrophy Patients

    The most common genetic cause of death in young children is a neuromuscular disease called spinal muscular atrophy (SMA). While the disease is known to result from mutations in a single gene - SMN1 - the mechanisms by which a lack of SMN1 protein causes SMA's degenerative symptoms are still poorly understood. Survival of patients is dependent on the amount of SMN1 protein present in the body so elevating those levels could lead to an effective treatment. Recent work from HSCI Executive Committee Member Lee Rubin used an image-based method to screen for molecules that increase SMN1 protein levels in the body. Through this method, the team identified a signaling pathway crucial to the maintenance of SMN1 protein levels. The pathway consists of a series of chemicals that not only allows for increased SMN1 protein levels, but also blocks cell death in low SMN1-level conditions. Affording a keener understanding of SMA biology, this research also presents a potential future treatment strategy for SMA patients.

    Makhortova, N.; Hayhurst, M.; Cerqueira, A.; Sinor-Anderson, A.; Zhao, W.; Heiser, P.; Arvanites, A.; Davidow, L.; Waldon, Z.; Steen, J.; Lam, K.; Ngo, H.; Rubin, L. (2011) A Screen for Regulators of Survival of Motor Neuron Protein Levels Nature Chemical Biololgy 7, 544-552. 

  • Know Your Destiny: A Signal for Cellular Differentiation

    Pluripotent cells have the ability to transform into any other kind of cell in the body, such as blood, bone, or muscle cells. In the earliest stages of life, pluripotent progenitor cells migrate into one of two "germ layers:" the mesendoderm (ME) and the neural ectoderm (NE) will eventually give way to all the organs in the body. But how does a cell know which germ layer it will become a part of? What signals help guide a cell to one fate or another and how does the cell know how to interpret those signals? Recent work from HSCI Principal Faculty members Sharad Ramanathan and Alexander Meissner begins to answer these questions. The team sifted through hundreds of molecules responsible for maintaining the pluripotent state, and identified just two that increase in concentration when a cell migrates into either the ME or NE. A series of subsequent experiments confirmed these two molecules as crucial regulators of differentiation. By monitoring the levels of these two molecules, future research may shed light on a broad array of cellular processes and the path that cells take in the course of their development.
        
    Thomson, M.; Liu, S.; Zou, L.; Smith, Z.; Meissner, A.; Ramanathan, S. (2011) Pluripotency Factors in Embryonic Stem Cells Differentiate into Germ Layers Cell 145, 875-889. 

  • The Secret Language of Cells

    Cells have their own language for communicating with one another, involving an array of molecular signals. In order to improve biological research and treatment techniques, scientist need to learn that lingo. For example, mesenchymal stem cells (MSCs) have shown great potential to treat a variety of pathologies, including inflammation and tissue damage, but many experiments have failed, partly due to a limited understanding of how they communicate with their environment. In order for stem-cell generated tissue transplants to be successful, biologists must understand how donor cells will interact with their host. Recent work from a team of HSCI researchers, lead by Principal Faculty member Jeffrey Karp, introduces new technology that translates that cellular language into visual signals, affording scientists a better understanding of how transplanted cells respond to their new environment. The team tagged MSCs with a sensor molecule that changes conformation in the presence of certain other molecules causing it to glow. The sensor used in this study can be manipulated to respond to a variety of specific molecular cues, allowing the technology to be broad-reaching in its impact. The group is also working to develop a molecular switch based on their new sensor. This would allow researchers to track the real-time rise and fall of signals after the introduction of non-native cells, giving a realistic view of what happens in the body following transplants.

    Zhao, W.; Schafer, S.; Choi, J.; Yamanaka, Y.; Lombardi, M.; Vose, S.; Carlson, A.; Phillips, J.; Teo, W.; Droujinine, I.; Cui, C.; Jain, R.; Lammerdin, J.; Love, J.; Lin, C.; Sarkar, D.; Karnik, R.; Karp, J. (2011) Cell-Surface Sensors for Real-Time Probing of Cellular Environments Nature Nanotechnology 6, 524-531.