Looking like necklaces stacked on a dresser, these bright, amorphous loops show the outlines of yeast proteins that make up the spindle pole, a cellular component found in organisms as diverse as yeast and humans. Each cell starts with a single spindle pole, which must somehow duplicate to form the pair that works together to pull matching chromosomes apart during cell division. Scientists don’t completely understand how this duplication occurs, but they do know that errors in spindle pole copying can lead to a number of health conditions, including cancer. Continue reading “Cool Image: Tracing Proteins in Action”
The planarian has a power few creatures can match. Remove its head, its tail or nearly any of its body parts, and this aquatic flatworm will simply grow it back. Humans can’t do that, of course. And yet many of the genes that help the planarian regenerate are also found in us. To learn more about this tiny marvel, we “interviewed” a representative. Continue reading “Interview With a Worm: We’re Not So Different”
When daylight savings time ends this Sunday, we’ll need to adjust every clock in our homes, cars and offices. Our internal clocks will need to adjust too.
The body has a master clock in the brain, as well as others in nearly every tissue and organ. These biological clocks drive circadian rhythms, the physical, mental and behavioral changes we experience on a roughly 24-hour cycle. Your hunger in the morning and sleepiness at night, for example, are caused partly by clock gears in motion. These gears can get out of synch with the day-night cycle when the time changes or when we travel through time zones.
Bacteria hold a vast reservoir of compounds with therapeutic potential. They use these compounds, known as secondary metabolites, to protect themselves against their enemies. We use them in many antibiotics, anti-inflammatories and other treatments.
Scientists interested in developing new medicines have no shortage of places to look for secondary metabolites. There are an estimated 120,000 to 150,000 bacterial species on Earth. Each species is capable of producing hundreds of secondary metabolites, but often only under specific ecological conditions. The challenge for researchers is figuring out how to coax the bacteria to produce these compounds.
Now, Brian Bachmann and John McLean of Vanderbilt University and their teams have shown that by creating “fight clubs” where bacteria compete with one another, they can trigger the bacteria to make a wide diversity of molecules, including secondary metabolites. Continue reading “Bacterial ‘Fight Clubs’ and the Search for New Medicines”
Roll out the red carpet and shine up your shoes—it’s “award season” for science. The biggest prizes: powerful glimpses into fundamental life processes that can yield deeper understanding of health and disease.
For instance, the 2015 Albert Lasker Basic Medical Research Award that’s being presented today highlights the seminal work of two scientists on the DNA-damage response, a mechanism that protects the genomes of all living organisms. Chemicals, radiation and duplication errors during cell division are constantly harming our genetic material. Healthy cells respond with a complex network of proteins that work together to mend the damage and halt cell division until repairs are complete. If injury is beyond repair, the proteins trigger cell death. Errors in the DNA-damage response can lead to cancer, neurodegenerative disorders and immune deficiencies.
The scientists recognized today took important steps toward elucidating the mechanics of the DNA-damage response. Evelyn Witkin of Rutgers University established its existence and its basic features in bacteria. Continue reading ““Award Season” for Science”
We asked the heads of our scientific divisions to tell us about some of the big questions in fundamental biomedical science that researchers are investigating with NIGMS support. This article is the second in an occasional series that explores these questions and explains how pursuing the answers could advance understanding of important biological processes.
For some health conditions, the cause is clear: A single altered gene is responsible. But for many others, the path to disease is more complex. Scientists are working to understand how factors like genetics, lifestyle and environmental exposures all contribute to disease. Another important, but less well-known, area of investigation is the role of chance at the molecular level.
One team working in this field is led by John Tyson at Virginia Tech. The group focuses on how chance events affect the cell division cycle, in which a cell duplicates its contents and splits into two. This cycle is the basis for normal growth, reproduction and the replenishment of skin, blood and other cells throughout the body. Errors in the cycle are associated with a number of conditions, including birth defects and cancer. Continue reading “How Cells Manage Chance”
By showing that our immune and nervous systems are connected, Kevin J. Tracey of the North Shore-LIJ Health System’s Feinstein Institute for Medical Research helped launch a new discipline called bioelectronic medicine. In this field, scientists explore how to use electricity to stimulate the body to produce its own disease-fighting molecules.
I spoke with Tracey about his research, the scientific process and where bioelectronic medicine is headed next.
How did you uncover the connection between our immune and nervous systems?
My lab was testing whether a chemical we developed called CNI-1493 could stop immune cells from producing inflammation-inducing molecules called TNFs in the brain of rats during a stroke. It does. But we were surprised to find that this chemical also affects neurons, or brain cells. The neurons sense the chemical and respond by sending an electrical signal along the vagus nerve, which runs from the brain to the internal organs. The vagus nerve then releases molecules that tell immune cells throughout the body to make less TNF. I’ve named this neural circuit the inflammatory reflex. Today, scientists in bioelectronic medicine are exploring ways to use tiny electrical devices to stimulate this reflex to treat diseases ranging from rheumatoid arthritis to cancer. Continue reading “From Basic Research to Bioelectronic Medicine”
We asked the heads of our scientific divisions to tell us about some of the big questions in fundamental biomedical science that researchers are investigating with NIGMS support. This article is the first in an occasional series that will explore these questions and explain how pursuing the answers could advance understanding of important biological processes.
Cells are faced with many decisions: When’s the best time to produce a new protein? To grow and split into two? To treat another cell as an invader? Scientists are working to understand how cells make these and many other decisions, and how these decisions contribute to health and disease.
An active area of research on cell decisions focuses on allorecognition, the ability of an organism to distinguish its own cells from those of another. Immune cells use a system called the major histocompatibility complex (MHC) to identify which cells belong to the body and which are foreign. The particular set of MHC proteins on the outer surface of a cell helps immune cells decide whether it does not belong and should be attacked.
But the system isn’t perfect. Invading pathogens can go undetected, and the body can mistake its own cells for intruders. Continue reading “How a Cell Knows Friend From Foe”
Hunting for the cause of a disease can be like tracing a river back to its many sources. Myriad factors, large and small, may contribute to a condition. One approach to the search focuses on the massive amounts of genomic and other biological data that scientists are gathering in the course of their studies. To examine this data and look for meaningful patterns and other clues, scientists turn to bioinformatics, a field focused on the development of analytical methods and software tools.
Here are a few examples of how National Institutes of Health-funded scientists are using bioinformatics to dig deeply into data and learn more about the development of diseases, including Huntington’s, preeclampsia and asthma.
The cause of Huntington’s disease, a degenerative neurological disorder with no known cure, may appear simple. It begins with a change in a single gene that alters the shape and functioning of the huntingtin protein. But this protein, whether in its normal or altered form, does not act alone. It interacts with other proteins, which in turn interact with others.
A research team led by Robert Hughes of the Buck Institute for Research on Aging set out to understand how this ripple effect contributes to the breakdown in normal cellular function associated with Huntington’s disease. The scientists used experimental and computational approaches to map a network of 2,141 proteins that interact with the huntingtin protein either directly or through one other protein. They found that many of these proteins were involved in cell movement and intercellular communication. Understanding how the huntingtin protein leads to mistakes in these cellular processes could help scientists pursue new approaches to developing treatments. Continue reading “Digging Deeply Into Data for the Causes of Disease”
Scientists may screen billions of chemical compounds before uncovering the few that effectively treat a disease. But identifying compounds that work is just the first step toward developing a new therapy. Scientists then have to determine exactly how those compounds function.
Different cancer therapies attack cancer cells in distinct ways. For example, some drugs kill cancer cells by causing their outer membranes to rapidly rupture in a process known as necrosis. Others cause more subtle changes to cell membranes, which result in a type of programmed cell death known as apoptosis.
If researchers could distinguish the membrane alterations of chemically treated cancer cells, they could quickly determine how that chemical compound brings about the cells’ death. A new sensor developed by a research team led by Vincent Rotello of the University of Massachusetts Amherst can make these distinctions in minutes. Continue reading “A Bright New Method for Rapidly Screening Cancer Drugs”