Dr. Chill's Lab
Head - Bio NMR Lab
Dr. Jordan Chill is a returning scientist from the National Institutes of Health (NIH) in Maryland, and Senior Lecturer in BIU's Department of Chemistry. In his lab, Chill uses Nuclear Magnetic Resonance (NMR) spectroscopy to study protein structure, with special emphasis on membrane-associated proteins (MPs).
These proteins are extremely important as guardians of the cell and have many biological roles, yet defy structural study because they must be examined in a cumbersome hydrophobic medium which mimics the membrane.
Chill's team applies a combination of protein expression and sample preparation methods to create detergent- or lipid-solubilized MPs which can be studied using NMR, and then tries to shed light on their structure, dynamics and function.
Alongside the effort to elucidate molecular mechanisms of interesting biological systems, they are attempting to characterize the biophysics of proteins within biological membranes by studying suitably designed model systems.
Drug Discovery, Design, and Delivery Research with Membrane-Embedded Proteins
Some 70% of drugs target proteins associated with the cellular membrane. However, the physical shape of membrane proteins is almost completely unknown. Chill seeks to close this gap, by acquiring reliable structural data about membrane-embedded proteins.
In one of his projects, he uses NMR techniques to map the binding interface between two proteins associated with multiple sclerosis – something that will aid in the design of MS inhibitors with limited side-effects. With his team he has created a hybrid potassium channel that mimics a human channel found on MS-causing immune cells, yet can be produced in large amounts by bacteria.
They are now using this system to identify peptides – inspired by naturally-occurring molecules – that will bind tightly and selectively to this particular channel, effectively shutting down the renegade immune response, while allowing other potassium channels to continue normal activity.
Membrane Permeability and Viral Infection
Chill's group is also looking at the molecular mechanisms involved in the ability of viral particles to enter through the membrane and infect the cell. Using a membrane-mimicking model, they are examining the activity of two proteins – each containing a trans-membrane domain – that must assemble into a single structure for infection to occur.
Their first daunting task is to efficiently manufacture these peptides using recombinant expression technology, in order to label them with NMR-active nuclei. Once this is accomplished, Chill and his team aim to determine the molecular interactions that mediate this process.
Ultimately, he hopes to use this information to suggest possible inhibitors that will halt progression of the disease. NMR methods are the ideal approach for tackling these complex systems, due to their ability to characterize the interaction between proteins, which has rapidly developed over the past decade.
Equipped with a state-of-the-art magnetic spectrometer, Chill and his team are confident that they can contribute to a better understanding of these systems at the molecular level, facilitating future drug-design efforts.