Recent News

Jianhan Chen Lab Discovers New Channel-Gating Mechanism and Receives New NIH Grant

Computational biophysicists are not used to making discoveries, says Jianhan Chen, Professor of Chemistry and Biochemistry & Molecular Biology, so when he and colleagues cracked the secret of how cells regulate Big Potassium (BK) channels, they thought it must be a computational artifact. But after many simulations and tests, they convinced themselves that they have identified the BK gating mechanism that had eluded science for many years.

BK channels are important in neuronal and muscle functions and are associated with pathogenesis of hypertension, autism, epilepsy, stoke, asthma, etc. A key puzzle has been trying to understand how cells close, or gate, BK channels, which have an unusually large central pore. “There were a lot of hypotheses, but no answers,” Chen notes. Now in Nature Communications, his team demonstrates that a phenomenon known as “hydrophobic dewetting” gives rise to a vapor phase in the pore’s central cavity to block intracellular access to the selectivity filter.

Chen’s work on BK channels has also led to a new four-year, $2.9 million grant from NIH’s National Heart, Lung, and Blood Institute. The collaborative team includes Jianmin Cui at Washington University, St. Louis, Chen at UMass Amherst and Xiaoqin Zou at the University of Missouri.

Martin Lab Applies State of the Art Tools in New Ways, to Advance RNA Therapeutics and Nanotechnology

The Martin lab studies the enzyme used by thousands of researches for synthesizing RNA in the test tube. New work published in the journal Nucleic Acids Research (and highlighted as a “Breakthrough Article”) characterizes undesired (and at times, technology-limiting) impurities in that synthesis, providing a mechanistic understanding that will help the design of solutions. The work exploits a modern tool in genomics, RNA-Seq, but applies it in new ways. While gel electrophoresis has been the tool of choice for the past century, this new approach represents a huge advance, identifying not just lengths of RNA, but exact sequences and sequence distributions.

RNA therapeutics companies are already taking notice, particularly those invested in mRNA therapeutics, since chemical synthesis of long RNAs is not a possibility. Impurities in the RNA trigger a potentially lethal immune response, and have been holding back major advances in what could be a key, new therapeutic approach, with wide applicability. This work does not provide the solution, but provides key understandings that may well lead to solutions.

Jianhan Chen Receives Grant to Study ‘Floppy’ Proteins

Jianhan Chen recently received a four-year, $600,000 grant from the National Science Foundation to study a newly recognized class of proteins with highly flexible three-dimensional (3D) structural properties, in particular some extra-floppy ones called intrinsically disordered proteins (IDPs).

Proteins are macromolecules that control nearly all aspects of cell function from response to external stimuli to control of cell cycle and cell fate decisions, Chen explains. He adds that IDPs are unusual because while most proteins adopt stable 3D structures to do their work in the cell, IDPs instead remain structurally disordered, that is, extremely flexible. They are believed to account for about one-third of all eukaryotic proteins and are key components of cellular signaling and regulatory networks.

Scientists now believe that by staying flexible, IDPs have an advantage in interacting with other proteins and each other, perhaps because the floppy state lets them respond faster than a more rigid structure, or lets them interact with a wider variety of molecules, or both, Chen says.

Jeanne Hardy Wins Inaugural Mahoney Life Sciences Prize for High-Impact, Applied Research

Jeanne Hardy, associate professor of chemistry, whose research focuses on a key protein linked to neurological disorders such as Alzheimer’s disease, is being recognized with the inaugural Mahoney Life Sciences Prize at the University of Massachusetts Amherst. A panel of expert judges from the life sciences sector observed that the “biomedical implications are significant” and “this could turn out to be one of ‘the’ pivotal studies in the effort to combat Alzheimer’s.” Hardy will receive the prize and present her research with life sciences experts and UMass officials and scientists at a breakfast ceremony on June 19 at the UMass Club in Boston. “Professor Hardy’s research rose to the top of three highly competitive rounds of review,” said Tricia Serio, dean of the College of Natural Sciences. “Her work exemplifies the outstanding translational research for which our faculty are well known.”

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