Biomedical Beat Blog – National Institute of General Medical Sciences
Follow the process of discovery
Many researchers who search for anti-cancer drugs have labs filled with chemicals and tissue samples. Not Rommie Amaro. Her work uses computers to analyze the shape and behavior of a protein called p53. Defective versions of p53 are associated with more human cancers than any other malfunctioning protein.
While DNA acts as the hard drive of the cell, storing the instructions to make all of the proteins the cell needs to carry out its various duties, another type of genetic material, RNA, takes on a wide variety of tasks, including gene regulation, protein synthesis, and sensing of metals and metabolites. Each of these jobs is handled by a slightly different molecule of RNA. But what determines which job a certain RNA molecule is tasked with? Primarily its shape. Julius Lucks
, a biological and chemical engineer at Northwestern University, and his team study the many ways in which RNA can bend itself into new shapes and how those shapes dictate the jobs the RNA molecule can take on.
Continue reading “Interview With a Scientist—Julius Lucks: Shape Seeker”
Cataloging the human microbiome—the complete collection of bacteria, fungi, archaea, protists, and viruses that live in and on our bodies—is an enormous task. Most estimates put the number of organisms who call us home on par with the number of our own cells. Imagine trying to figure out how the billions of critters influence each other and, ultimately, impact our health. Elhanan Borenstein, a computer scientist-cum-genomicist at the University of Washington, and his team are not only tackling this difficult challenge, they are also trying to obtain a systems-level understanding of the collective effect of all of the genes, proteins, and metabolites produced by the numerous species within the microbiome.
Continue reading “Interview With a Scientist—Elhanan Borenstein: Metagenomics Systems Biology”
You’ve likely heard some variation of the statistic that there are at least as many microbial cells in our body as human cells. You may have also heard that the microscopic bugs that live in our guts, on our skins, and every crevice they can find, collectively referred to as the human microbiome, are implicated in human health. But do these bacteria, fungi, archaea, protists, and viruses cause disease, or are the specific populations of microbes inside us a result of our state of health? That’s the question that drives the research in the lab of Andrew Goodman , associate professor of microbial pathogenesis at Yale University.
For more than 30 years, NIGMS has supported the structural characterization of human immunodeficiency virus (HIV) enzymes and viral proteins. This support has been instrumental in the development of crucial drugs for antiretroviral therapy such as protease inhibitors. NIGMS continues to support further characterization of viral proteins as well as cellular and viral complexes. These complexes represent the fundamental interactions between the virus and its host target cell and, as such, represent potential new targets for therapeutic development.
In this third in a series of three video interviews with NIGMS-funded researchers probing the structure of HIV, Michael Summers, professor of biochemistry at the University of Maryland, Baltimore County, discusses his use of nuclear magnetic resonance (NMR) technology to study HIV. Of recent interest to Summers has been using NMR to investigate how HIV’s RNA enables the virus to reproduce. His goals for this line of research are to develop treatments against HIV as well as learning how to best engineer viruses to deliver helpful therapies to individuals with a variety of diseases.
For more than 30 years, NIGMS has supported the structural characterization of human immunodeficiency virus (HIV) enzymes and viral proteins. This support has been instrumental in the development of crucial drugs for antiretroviral therapy such as protease inhibitors. NIGMS continues to support further characterization of viral proteins as well as cellular and viral complexes. These complexes represent the fundamental interactions between the virus and its host target cell and, as such, represent potential new targets for therapeutic development.
In this second in a series of three video interviews with NIGMS-funded researchers probing the structure of HIV, Wes Sundquist, professor of biochemistry at the University of Utah, discusses his lab’s studies of how HIV uses factors in host cells to replicate itself. In particular, Sundquist focuses on the ESCORT pathway that enables HIV to leave infected cells and spread infection elsewhere.
Continue reading “Interview with a Scientist: Wes Sundquist, How the Host Immune System Fights HIV”
For more than 30 years, NIGMS has supported the structural characterization of human immunodeficiency virus (HIV) enzymes and viral proteins. This support has been instrumental in the development of crucial drugs for antiretroviral therapy such as protease inhibitors. NIGMS continues to support further characterization of viral proteins as well as cellular and viral complexes. These complexes represent the fundamental interactions between the virus and its host target cell and, as such, represent potential new targets for therapeutic development.
Continue reading “Interview With a Scientist: Irwin Chaiken, Rendering HIV Inert”
The first known descriptions of cancer come from ancient Egypt more than 3,500 years ago. Early physicians attributed the disease to several factors, including an imbalance in the body’s humoral fluids, trauma, and parasites. Only in the past 50 years or so have we figured out that mutations in critical genes are often the trigger. The sea lamprey, a slimy, snake-like blood sucker, is proving to be an ideal tool for understanding these mutations.
The sea lamprey, often called the jawless fish, is an ancient vertebrate whose ancestor diverged from the other vertebrate lineages (fish, reptiles, birds and mammals) more than 500 million years ago. Jeramiah Smith, associate professor of biology at the University of Kentucky, has discovered that lamprey have two separate genomes: a complete genome specific to their reproductive cells, consisting of 99 chromosomes (humans have 23 pairs) and another genome in which about 20 percent of genes have been deleted after development. Using the lamprey model, Smith and his colleagues have learned that many of these deleted genes—such as those that initiate growth pathways—are similar to human oncogenes (i.e., cancer-causing genes).
One day last fall, molecular biologist Laura Landweber surveyed the Princeton University lab where she’d worked for 22 years. She and her team members had spent many hours that day laboriously affixing yellow Post-it notes to the laboratory equipment—microscopes, centrifuges, computers—they would bring with them to Columbia University, where Landweber had just been appointed full professor. Each Post-it specified the machinery’s location in the new lab. Items that would be left behind—glassware, chemical solutions, furniture, office supplies—were left unlabeled.
As Landweber viewed the lab, decorated with a field of sunny squares, her thoughts turned to another sorting process—the one used by her primary research subject, a microscopic organism, to sift through excess DNA following mating. Rather than using Post-it notes, the creature, a type of single-celled organism called a ciliate, uses small pieces of RNA to tag which bits of genetic material to keep and which to toss.
Landweber is particularly fond of Oxytricha trifallax, a ciliate with relatives that live in soil, ponds and oceans all over the world. The kidney-shaped cell is covered with hair-like projections called cilia that help it move around and devour bacteria and algae. Oxytricha is not only bizarre in appearance, it’s also genetically creative.
Unlike humans, whose cells are programmed to die rather than pass on genomic errors, Oxytricha cells appear to delight in genomic chaos. During sexual reproduction, the ciliate shatters the DNA in one of its two nuclei into hundreds of thousands of pieces, descrambles the DNA letters, throws most away, then recombines the rest to create a new genome.
Landweber has set out to understand how—and possibly why—Oxytricha performs these unusual genomic acrobatics. Ultimately, she hopes that learning how Oxytricha rearranges its genome can illuminate some of the events that go awry during cancer, a disease in which the genome often suffers significant reorganization and damage.
Oxytricha’s Unique Features
Oxytricha carries two separate nuclei—a macronucleus and a micronucleus. The macronucleus, by far the larger of the two, functions like a typical genome, the source of gene transcription for proteins. The tiny micronucleus only sees action occasionally, when Oxytricha reproduces sexually.
What really makes Oxytricha stand out is what it does with its DNA during the rare occasions that it has sex. When food is readily available, Oxytricha procreates without a partner, like a plant grown from a cutting. But when food is scarce, or the cell is stressed, it seeks a mate. When two Oxytricha cells mate, the micronuclear genomes in each cell swap DNA, then replicate. One copy of the new hybrid micronucleus remains intact, while the other breaks its DNA into hundreds of thousands of pieces, some of which are tagged, recombined, then copied another thousand-fold to form a new macronucleus. Continue reading “Genomic Gymnastics of a Single-Celled Ciliate and How It Relates to Humans”
The stunning pigmentation of tigers, the massive jaws of sharks, and the hyper-acute vision of eagles. These and other remarkable features of higher organisms (vertebrates) derive from a small group of powerful cells, called neural crest cells, that arose more than 500 million years ago. Molecular biologist Carole LaBonne 
of Northwestern University in Illinois studies how neural crest cells help give rise to these important vertebrate structures throughout development.
Very early during embryonic development, stem cells differentiate into different layers: mesoderm, endoderm, and ectoderm. Each of these layers then gives rise to different cell and tissue types. For example, the ectoderm becomes skin and nerve cells. Mesoderm turns into muscle, bone, fat, blood and the circulatory system. Endoderm forms internal structures such as lungs and digestive organs.
These three layers are present in vertebrates—animals with a backbone and well-defined heads, such as fish, birds, reptiles, and mammals—as well as animals without backbones, such as the marine-dwelling Lancelets and Tunicates (referred to as non-vertebrate chordates). Unlike cells in these layers, neural crest cells, which are found only in vertebrates, don’t specialize until much later in development. The delay gives neural crests cells the extra time and flexibility to sculpt the complex anatomical structures found only in vertebrate animals.
Scientists have long debated how neural crest cells manage to finalize their destiny so much later than all other cell types.
Using the frog Xenopus as a model system, LaBonne and her colleagues performed a series of experiments that revealed the process and identified key genes that control it.
In this video, LaBonne describes the power of neural crest cells and how they can be useful for studies of human health, including how cancer cells can metastasize, or migrate, throughout the body.
Dr. LaBonne’s research is funded in part by NIGMS grant 5R01GM116538.