Rohit V. Pappu, Ph.D.

The Biophysical Society (BPS) recently named a bioengineer from Washington University in St. Louis as one of its 2019 Society Fellows.

Rohit Pappu, the Edwin H. Murty Professor of Engineering in the School of Engineering & Applied Science, will be honored along with the other BPS Fellows during the society’s annual meeting in March.

The designation honors the society’s distinguished members who have demonstrated excellence in science, contributed to the expansion of the field of biophysics, and supported the Biophysical Society throughout their careers.

Membraneless organelles are tiny droplets inside a single cell, thought to regulate everything from division, to movement, to its very destruction. A better understanding of these mysterious structures could hold the key to unlocking a whole host of medical conditions, including developmental disorders, childhood cancers and age-related diseases.

New research from the School of Engineering & Applied Science at Washington University in St. Louis, published in the journal eLife, uncovers the principles underlying the formation and organization of membraneless organelles.

“If our theory and modeling are correct, we ought to be able to design these organelles in the way we want to,” said Rohit Pappu, the Edwin H. Murty Professor of Engineering in the Department of Biomedical Engineering… Continue reading.

Huntington’s disease is a progressive, fatal neurodegenerative disorder that is caused by mutations in one specific gene called huntingtin (Htt). In the 20-plus years since the Htt gene was identified, researchers have focused on the protein encoded by the Htt gene, called Httex1. This protein accumulates in the brains of Huntington’s disease patients, and the prevailing hypothesis has been that it undergoes a dramatic structural change when a repetitive tract of the amino acid glutamine mutates into an aberrantly long region known as the mutationally expanded polyglutamine (polyQ) tract.

Now, for the first time, the team of Hilal A. Lashuel at Ècole Polytechnique Fèdèrale de Lausanne (EPFL) in Switzerland; Edward A. Lemke at the European Molecular Biology Laboratory (EMBL) in Germany; and Rohit V. Pappu at Washington University in St. Louis has uncovered a detailed structural description of Htt as a function of polyQ length. The work was published recently in the Journal of the American Chemical Society… Continue reading.

Engineering new materials holds enormous potential to improve and advance the global community. Breakthroughs in medicine, defense and clean energy could be achieved by designing polymeric materials with a whole host of abilities and properties.

To push this emerging field forward, the National Science Foundation (NSF) set up an initiative called Designing Materials to Revolutionize and Engineer our Future (DMREF). In August, DMREF awarded a four-year, $1.4 million grant to a team consisting of researchers from the engineering schools of Washington University in St. Louis and Duke University. The initiative awards grants to researchers at the forefront of materials advancement, enabling them to push science, stretch their imaginations in the quest to streamline the development of new soft materials, and predict and tune their properties for both existing and novel applications.

“You can imagine making an adhesive that will also have the strength of steel,” said Rohit Pappu, the Edwin H. Murty Professor of Engineering at Washington University’s School of Engineering & Applied Science. “Or perhaps something that will flow like toothpaste but also have the potential to be used as a miniature bioreactor. We could use new materials for drug delivery, drug storage, artificial tissues, and other applications we haven’t thought of yet.”

Researchers Ashutosh Chilkoti, the Alan L. Kaganov Professor of Biomedical Engineering and chair of the Department of Biomedical Engineering, and Stefan Zauscher, the Sternberg Family Professor of Mechanical Engineering & Materials Science, comprise the Duke team… Continue reading.

By age 2, most children have been infected with respiratory syncytial virus (RSV), which usually causes only mild cold symptoms. But people with weakened immune systems, such as infants and the elderly, can face serious complications, including pneumonia and – in some cases – death.

Now, scientists studying the virus, led by researchers at Washington University School of Medicine in St. Louis, have found clues to how RSV causes disease. They mapped the molecular structure of an RSV protein that interferes with the body’s ability to fight off the virus. Knowing the structure of the protein will help them understand how the virus impedes the immune response, potentially leading to a vaccine or treatment for this common infection.

“We solved the structure of a protein that has eluded the field for quite some time,” said Daisy Leung, an assistant professor of pathology and immunology, and of biochemistry and molecular biophysics at Washington University School of Medicine in St. Louis, and the study’s co-senior author. “Now that we have the structure, we’re able to see what the protein looks like, which will help us define what it does and how it does it. And that could lead, down the road, to new targets for vaccine or drug development.”

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To test their hypothesis, the researchers created different versions of the NS1 protein, some with the alpha 3 helix region intact, and some with it mutated. In collaboration with others – Rohit Pappu, the Edwin H. Murty Professor of Biomedical Engineering, Michael Holtzman, MD, the Selma and Herman Seldin Professor of Medicine, Maxim Artyomov, an assistant professor of pathology and immunology, and Christopher Basler of Georgia State University – they tested the functional impact of helix 3 and created a set of viruses containing the original or the mutant NS1 genes, and measured the effect on the immune response when they infected cells with these viruses.

They found that the viruses with the mutated helix region did not suppress the immune response while the ones with the intact helix region did… Continue reading.

New experimental and theoretical approaches ‘dive into the pool’ of membranes organelles

Inside each and every living cell, there are miniscule structures called membraneless organelles. These tiny powerhouses use chemistry to cue the inner workings of a cell — movement, division and even self-destruction.

A collaboration between engineers at Princeton University and Washington University in St. Louis has developed a new way to observe the inner workings and material structure of these vitally important organelles. The research, published today in Nature Chemistry, could lead to a host of new scientific applications, as well as a better understanding of diseases such as cancer, Huntington’s and ALS.

“They’re like little drops of water: They flow, they have all the properties of a liquid, similar to raindrops,” said Rohit Pappu, the Edwin H. Murty Professor of Engineering at Washington University’s School of Engineering & Applied Science. “However, these droplets are comprised of protein that come together with RNA (ribonucleic) molecules.”

In the past, peering into organelles has proven difficult, due to their tiny size. Clifford Brangwynne, associate professor in chemical and biological engineering at Princeton’s School of Engineering and Applied Science, and his collaborators, developed a new technique — called ultrafast scanning fluorescence correlation spectroscopy or usFCS — to get an up-close assessment of the concentrations within and probe the porosity of facsimiles of membraneless organelles. The approach uses sound-waves to control a microscope’s ability to move and then obtain calibration-free measurements of concentrations inside membraneless organelles… Continue reading.

WASHINGTON, D.C.— The American Institute for Medical and Biological Engineering (AIMBE) has announced the pending induction of Rohit V. Pappu, Ph.D., Edwin H. Murty Professor of Engineering, Biomedical Engineering, Washington University in St. Louis, to its College of Fellows. Dr. Pappu was nominated, reviewed, and elected by peers and members of the College of Fellows For outstanding contributions to protein engineering and design and the molecular basis of neurodegeneration through advances in computational biology.