Exploring the ‘Dark Matter’ of the Cell

Tom Maresca recently received a four-year, $1.3 million grant renewal from the National Institute of General Medical Sciences to use specialized tools to learn more about the less-studied inner universe of the cell.

There is a little-understood realm inside cells that cell biologist Tom Maresca likes to think of as the cell’s dark matter, something like the largely unknown stuff that is so abundant in space.

He explains that a foundational aspect of how scientists think about biology is called the structure-function paradigm, referring to how many proteins adopt specific and highly reproducible folded shapes that allow them to carry out their functions. For these, shape and function are inextricably linked. “These would be analogous to regular matter and they can be studied with conventional biochemical methods and techniques like X-ray crystallography and cryo-electron microscopy,” Maresca says.

“But there are also many proteins that are predicted to have no specific structure, and they’re not as easy to study as well-folded proteins. They’re called intrinsically disordered proteins, which means they are unstructured,” he adds.

Sometimes referred to as the Dark Proteome, these shapeless proteins “appear to be very abundant, we just don’t know much about them. There’s been tremendous progress in understanding structure-function; now we hope to make progress in this other important area of how unstructured proteins function.”

For the new grant, Maresca and colleagues will collaborate with biophysicist Nathan Derr at Smith College.

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Peg Riley Gave a "Fireside Chat" at the Precision Medicine Conference in Silicon Valley in January

Peg Riley was invited to give a "Fireside Chat" with Keith Yamamoto at the Precision Medicine Conference in Silicon Valley on January 22-24, 2020.

Keith R. Yamamoto is Vice Chancellor for Research, Executive Vice Dean of the School of Medicine, and Professor of Cellular and Molecular Pharmacology at the University of California, San Francisco, UCSF.

The Precision Medicine World Conference is the largest & original annual conference dedicated to precision medicine. PMWC’s mission is to bring together recognized leaders, top global researchers and medical professionals, and innovators across healthcare and biotechnology sectors to showcase practical content that helps close the knowledge gap between different sectors, thereby catalyzing cross-functional fertilization & collaboration in an effort to accelerate the development and spread of precision medicine.

HERE is the link to her chat!


Digital Life on Earth

Duncan Irschick is working on UMass Amherst’s Digital Life Project to create visual records of critically endangered species.

The Digital Life Project at the University of Massachusetts Amherst has been revolutionary in creating visual records of critically endangered species in ways that technology has never allowed before.

The project team modeled the first-ever 3D image of a southern right whale after researchers used aerial photography and drone videos to measure the mass and volume of whales. Previously, the only way to weigh any whale was by using a dead or stranded animal. Using its innovative Beastcam array, the team has also produced the world’s first accurate 3D image of the southern white rhino.

Led by Professor of Biology Duncan Irschick, the Digital Life Project has gathered a number of global collaborators. Documenting southern right whales as they gathered at their winter breeding grounds off the coast of Argentina involved participants from the Southern Right Whale Health Monitoring Program and the Aarhus Institute of Advanced Studies in Denmark. To create the visual of a rare southern white rhino, Irschick and team collaborated with the Perth Zoo in Australia, which volunteered its resident rhino, Bakari, to be photographed.

The resulting images are a valuable reference for researchers and conservationists. Measurements of live whales at sea offer information about how stressors affect the weight and physical condition of whales, as well as enabling accurate sedative dosing for whales who panic while entangled in fishing gear. All five species of rhinos are under extreme pressure worldwide, particularly from poaching for their horns. “It’s very special to photo-capture an animal like a rhino because they are a persecuted species,” comments Irschick.

Irschick and his colleagues have created several Beastcam rigs, including hand-held and tripod-mounted instruments in a variety of sizes for animals large and small. The original array consists of 10 fixed arms, each mounting three cameras for a 30-camera array. A variation of this method has even been used to photo-capture free-swimming sharks underwater! Animals located at the focal point of the array are modeled in 3D with special software. For Bakari the rhino, technicians and zoologists took photos from 360 degrees, and then a CGI artist animated the results, which were released last fall on World Rhino Day.

The UMass Amherst Digital Life Project makes its data and models publicly available as “an archive for animals,” says Irschick. The unique capabilities of the project are in demand, with models having been downloaded over 20,000 times since its inception.

As many species face down extinction, the Digital Life Project provides a compelling visual resource for those who want to intervene on behalf of their survival.

Click HERE to learn more!


New Green Technology from UMass Amherst Generates Electricity ‘Out of Thin Air’

The laboratories of electrical engineer Jun Yao and microbiologist Derek Lovley have developed a device that uses a natural protein to create electricity from moisture in the air, a new technology they say could have significant implications for the future of renewable energy, climate change and in the future of medicine. The device, called “Air-gen”, uses electrically conductive protein nanowires produced by the microbe Geobacter. The Air-gen connects electrodes to the protein nanowires in such a way that electrical current is generated from the water vapor naturally present in the atmosphere.

“We are literally making electricity out of thin air,” says Yao. “The Air-gen generates clean energy 24/7.” Lovely, who has advanced sustainable biology-based electronic materials over three decades, adds, “It’s the most amazing and exciting application of protein nanowires yet.”

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Bringing Visions to Light

The Jensen Lab is behind a single unmarked door in the basement of Morrill Science Center III.

In this lab, there are more than 6,000 of one of science’s most valuable models for studying human genetics and disease—the zebrafish. The tiny, striped members of the minnow family dart about in 200 small tanks on racks that are four rows deep.

In one particular tank, all of the zebrafish have lost their zebra; their typical five uniform, pigmented, horizontal stripes are gone. Called “crystals,” these creatures are a translucent pink, and you can see outlines of their backbones and the shadows of their tiny internal organs.

Light is actually a toxic insult upon life at the cellular level, especially on cells called photoreceptors that process light in the eye. “Their eyeballs are completely clear,” she explains. She hopes the light will degenerate, or damage, the cells. “It seems weird that we are trying to get the cells to die,” says Jensen. “But we need a model to get the cells to die so that we can understand why they die and then how to keep them alive.” Learning why the cells degenerate will improve our understanding of an eye disease that affects about one out of every 8–10 thousand young Americans: Stargardt disease.

Named for Karl Stargardt—the German ophthalmologist who first described the inherited eye disorder in 1909—Stargardt disease is a disorder of the retina that causes vision loss (though generally not complete blindness) during childhood or adolescence, though in some cases it doesn’t occur until adulthood. Vision loss progresses slowly over time in most people with the disease, from normal vision to legally blind. Currently, there is no treatment to delay or cure the disease.

Thanks to a grant from the Manning Innovation Program —a recent $40,000 gift to UMass for the support of translational research projects and the transfer of breakthroughs to the marketplace—Jensen hopes she is all the closer to finding a key that will unlock some of the secrets of Stargardt disease.

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