Advancing Structural Biology Research with 1.1 GHz NMR Spectrometer

 

With the world’s largest superconducting magnet, St. Jude Children’s Research Hospital aims to advance structural biology research. Operating at 1.1 GHz, the Nuclear Magnetic Resonance (NMR) Spectrometer will reveal previously unseen attributes of molecular biological systems. With this new installation, St. Jude will have NMR spectrometers operating at 400 MHz, 500 MHz, 600 MHz, 700 MHz, 800 MHz, 850 MHz and 1.1 GHz.

“This new addition will allow us to study biological systems that have been impossible. It's about having the right tool, the power and the resolution to go after these biological systems.”
-Babis Kalodimos, PhD, Chair of the Structural Biology Department

 
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  1. Okay, so, so what you see here, this is the most powerful magnet, superconducting magnet, in the world. Operates at the frequency of 1.1 gigahertz. This new addition will allow us to study biological systems that today have been impossible, so it's about of having the right tool, the power, and the resolution to go after these biological systems.

    This is very important, right because now, everybody knows that St. Jude is fully actually committed to investing in new technologies, being the first ones that get our hands and then test these new technologies. It's great also for St. Jude because a thing that will advance our research and that's very important, address biological questions, and then of course we all hope that one day, we can translate this one to actual cures for catastrophic diseases for kids.

The NMR Spectrometer will allow our scientists to explore:

  • Biomolecules, including proteins and the interior of cells
  • The molecular details of key biological processes, such as cell signaling and death, and DNA repair
  • Protein kinases and molecular chaperones involved in cancer and neurological diseases
  • Protein folding and misfolding
  • Phase separation
  • The detailed structures of proteins involved in these processes can be leveraged to help design new medicines, materials and diagnostic procedures.
 
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    Here at St. Jude Children's Research Hospital, we are committed to developing new technologies. To better understand the molecular basis of cancer and other catastrophic diseases and discover novel therapeutic approaches, researchers in the Department of Structural Biology use sophisticated tools [00:00:30] to reveal protein structure and function at the atomic level, with the ultimate goal of providing new cures to our patients.

    In a healthy human body, organs are constantly working to maintain body functions. In those organs, cells are involved in many different jobs and are constantly communicating with each other, a task known as cell signaling. To communicate, one cell releases a signaling molecule, for example, a hormone, into the space between cells. [00:01:00] The signaling molecule spreads and may bind to a receptor on the outside of a nearby cell. Then inside the cell, a chain of chemical messages is relayed that ultimately leads to some change within the cell. One type of chemical message is relayed by kinases, which are important proteins involved in coordinating most cellular activities, including cell survival, growth, and proliferation. The kinases are switched on and off [00:01:30] by different chemical messages in the cell to perform their functions.

    In a disease such as cancer, abnormal messages and cell signaling can be caused by changes in DNA pieces called genes. For instance, in chronic myelogenous leukemia, a cancer of the bone marrow, a piece of one chromosome breaks off and attaches to the end of another chromosome. This creates a new and abnormal gene, which leads to the production of an abnormal protein. [00:02:00] In chronic myelogenous leukemia, the abnormal protein called Bcr-Abl tyrosine-kinase does not respond to normal cell signals and is always active. As a result, bone marrow cells can grow and multiply unchecked, leading to chronic myelogenous leukemia. Drugs called tyrosine kinase inhibitors have been developed to bind to the Bcr-Abl protein and shut it off, allowing more normal cell signaling.

    This is just [00:02:30] one example of how drugs are designed to target specific abnormalities in cancers. Learning more about these abnormalities can help us better combat cancer. At St. Jude Children's Research Hospital, we use a special research technique called nuclear magnetic resonance spectroscopy or NMR spectroscopy to uncover the ways that cancer changes the body cells and chemical signals. In NMR spectroscopy, a biological sample is placed inside a magnet with a very [00:03:00] strong magnetic field. Then radio waves are directed at the sample. The interaction of the magnetic field and the radio waves with the biological sample causes unique signals to be emitted, which are measured by the NMR spectrometer.

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    By examining the signals, researchers can determine characteristics of important biomolecules, including their three-dimensional [00:03:30] structure and how they interact with other molecules in the cell. NMR spectroscopy provides unsurpassed technology to visualize how protein structures change over time and what happens when a drug binds to a receptor protein. In doing so, NMR spectroscopy helps researchers understand the mechanisms of disease and develop new drugs.

    At St. Jude Children's Research Hospital, our researchers are using NMR spectroscopy to study proteins involved in various forms of cancer. [00:04:00] St. Jude Children's Research Hospital is operating the most powerful magnet in the world, allowing us to have the clearest view of the proteins involved in cancers and the potential drugs to target them.

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Using NMR requires placing a biological sample inside a magnet with a very strong magnetic field. With radio and magnetic waves passing through it, the molecular sample emits signals that are then read by the spectrometer. Evaluating the signals can give researchers an idea of the three-dimensional shape of the molecule and how it might change in response to certain drugs. Researchers may then be able to develop more effective drugs to treat childhood cancer.

The 1.1 GHz instrument was extensively tested in Zurich by St. Jude researchers. The lab of Richard Kriwacki, PhD, collected data that were included in a Molecular Cell paper focusing on how toxic peptides associated with amyothrophic lateral sclerosis associate with a natural human protein.

Read the Findings.