HHMI's Understanding Biomedical Research Series - Video

Deciphering the Language of Sex

Wed, 20 Aug 2008 00:00:00 GMT

Even from a purely biological perspective, gender is a complex subject. Dr. David Page reviews the biological basis for sex, emphasizing the role of the sex chromosomes—the X and the Y—in mammals. He addresses the age-old question of why sex exists, and shows how sexual reproduction can have advantages over reproduction by cloning.

Hermaphrodites: The Safer Sex

Wed, 20 Aug 2008 00:00:00 GMT

What can a microscopic worm teach us about sex? Dr. Barbara Meyer emphasizes the value of studying the model organism C. elegans, a roundworm which has two sexes, but with a twist: they are male and hermaphrodite. Dr. Meyer explains how a single gene acts as a 'master switch' to activate a series of additional genes, resulting in a biochemical cascade that leads the worm to become male or hermaphrodite. The surprising differences between male and hermaphrodite lifestyles are also discussed.

Sex and Death: Too Much of a Good Thing

Wed, 20 Aug 2008 00:00:00 GMT

Genetic imbalances—such as those associated with Down syndrome in humans—are generally harmful. The number of copies of a given gene, the gene dose, can be very important. In the roundworm C. elegans, sex (male or hermaphrodite) is determined by the number of X chromosomes. Dr. Barbara Meyer explains how hermaphrodites control gene expression on their pair of X chromosomes to avoid having double the gene dose of males. By studying these sophisticated genetic systems in worms, scientists can learn more about related molecular pathways in mammals and humans.

Sexual Evolution: From X to Y

Wed, 20 Aug 2008 00:00:00 GMT

The presence of the Y chromosome triggers a human embryo to become male. Dr. David Page describes how the Y chromosome was once very much like every other gene-filled chromosome, but in the course of vertebrate evolution has lost almost every function except making males.

Endless Forms Most Beautiful

Wed, 10 Sep 2008 00:00:00 GMT

The Darwinian revolution was the first revolution in biology. University of Wisconsin--Madison's Sean B. Carroll traces the discovery of evolution through Charles Darwin's long voyage, many discoveries, and prodigious writings. Darwin introduced the concept of the 'fittest,' but how are the fittest made? The second revolution in biology was triggered by discoveries in genetics. Genetic variation, selection, and time combine to fuel the evolutionary process. The action of selection is now visible in DNA, both in preventing injurious changes and in favoring advantageous changes in traits.

Deconstructing Obesity

Wed, 20 Aug 2008 00:00:00 GMT

To approach the problem of obesity scientifically, we must first define and measure it. Dr. Friedman describes various methods for estimating obesity, including the body mass index, or BMI. He then explains the body's mechanisms for counting calories and accurately balancing food intake and energy consumption. Results from adoption and twin studies indicate a significant genetic contribution to human obesity. Dr. Friedman discusses his identification of the hormone leptin and its critical role in the control of body fat, further strengthening the case that obesity and weight control are largely a function of biology.

Understanding Fat: Syndrome X and Beyond

Wed, 10 Sep 2008 00:00:00 GMT

Environment, lifestyle, diet, marketing, and biology are all contributors to the obesity epidemic. How do our bodies balance the storage and burning of dietary fat? Fat carries information about how it should be used. Saturated fats are hard to break down, so they tend to get stored, while unsaturated fats are more readily consumed for energy. Too much stored fat leads to elevated blood glucose levels, which triggers insulin resistance -- the first step toward diabetes. Dr. Evans explores how diet and exercise influence the relationship between fat and muscle, promoting good health or precipitating diseases such as syndrome X, a disorder involving high blood pressure, heart disease, atherosclerosis, and insulin resistance.

Selection in Action

Wed, 10 Sep 2008 00:00:00 GMT

The products of natural, and human, selection are all around us. Humans have transformed wild plants into useful crops by selective breeding and produced domesticated animals with sizes and shapes very different from their wild ancestors. Genetic crosses suggest that relatively few genetic changes are needed to dramatically transform the shape and structure of plants and animals. Natural selection in wild populations can also generate amazing diversity in a surprisingly short amount of time. David M. Kingsley, Ph.D. explains the genetic studies suggest that major evolutionary changes are controlled by a few key genes.

Fossils, Genes, and Embryos

Wed, 10 Sep 2008 00:00:00 GMT

Recent studies have identified important genes that direct embryonic development. Specific developmental regulators help define larger body regions, such as heads and tails or the left and right sides of the body. David M. Kingsley explains how many key developmental genes are conserved among animals that look very different. A diversity of body forms can emerge from changing where and when these shared developmental regulators are expressed. Fossils suggest that similar developmental mechanisms were used in animals that evolved millions of years ago.

From Butterflies to Humans

Wed, 10 Sep 2008 00:00:00 GMT

The story of animal evolution is marked by key innovations such as limbs for walking on land, wings for flight, and color patterns for advertising or concealment. How do new traits arise? Sean B. Carroll, Ph.D. explores how new patterns evolve when 'old' genes learn new tricks. Old genes learning new tricks also apply to our own species and the evolution of traits that distinguish us from earlier hominids and other apes. Despite immense advances in evidence and understanding, there remains a societal struggle with the acceptance of our biological history and the evolutionary process.

Balancing the Fat Equation

Fri, 12 Sep 2008 00:00:00 GMT

A family of proteins called PPARs (peroxisome proliferator-activator receptors) controls how the body uses sugar and fat. PPAR-gamma drives the formation of fat cells and regulates the storage of fat. It encourages muscles to burn sugar and maintains insulin sensitivity. PPAR-delta regulates how muscles burn fat by stimulating cellular fat-burning pathways and increasing slow-twitch muscle mass, which primarily uses fat as an energy source. Mice that are engineered to produce an overactive version of this receptor in their muscle tissue remain sleek and lean. On a treadmill, these 'marathon mice' run twice as far as normal mice. Drugs that stimulate PPARs might help people slim down and improve health without altering appetite.

Exploring Obesity: From the Depths of the Brain to the Far Pacific

Wed, 10 Sep 2008 00:00:00 GMT

By studying the brains of obese mice, Dr. Friedman found that leptin rewires feeding circuits in the hypothalamus. From an evolutionary perspective, susceptibility to obesity can be an advantage or a disadvantage, depending on the resources available in an environment. Genes that predispose individuals to become obese might have evolved to help in surviving times of famine. Dr. Friedman uses population genetics, family history, and detailed medical records to study a population on the Pacific Island of Kosrae suffering an explosive increase in obesity. This research may identify new genes involved in regulating obesity and aid in developing treatments that benefit people on Kosrae and worldwide.

Biology in Four Dimensions

Wed, 20 Aug 2008 00:00:00 GMT

How do early birds get up in time to catch the worms? A clock in our brains helps us maintain daily, or circadian, rhythms. Dr. Joseph S. Takahashi discusses the natural history of biological rhythms and explains how he and other scientists have unraveled the complex workings of the body’s clocks. Biological clocks are key to understanding jet lag, various sleep disorders, and why teenagers have a hard time rising early.

Unwinding Clock Genetics

Wed, 20 Aug 2008 00:00:00 GMT

The fruit fly has taught scientists a great deal about the daily rhythms of animals and their internal biological clocks. Dr. Michael Rosbash explains how he and colleagues cloned the first gene identified as having an important role in the function of the clock. His work opened up the molecular analysis of biological clocks and represents one of the most advanced studies of how genes affect behavior.

Research Mechanics: Putting the Brakes on Cancer

Wed, 20 Aug 2008 00:00:00 GMT

Cancers are caused by an accumulation of mutations that alter the activity of genes involved in controlling cell birth, growth, and death. Some of these errors are inherited, but most occur after birth, triggered by environmental carcinogens or by mistakes during cell division. If cancer is likened to a car speeding out of control, cancer-causing mutations are like broken brakes, a stuck accelerator, or an inept mechanic. Dr. Vogelstein explains that although there are numerous kinds of cancer, all stem from alterations that allow cell division to outstrip cell demise.

Chaos to Cure: Bringing Basic Research to Patients

Wed, 20 Aug 2008 00:00:00 GMT

The identification of hundreds of genes involved in the formation and spread of cancer is leading to promising new methods for diagnosis, prevention, and treatment. In the case of colon cancer, researchers are developing genetic tests for detecting the cancer-causing mutations. Researchers are also investigating anti-cancer therapies that take advantage of the molecular differences between cancer cells and the normal cells surrounding them. In Dr. Vogelstein's lab, scientists are deploying specialized microbes to penetrate tumors, proliferate rapidly, and kill the cancer cells.

PERfect TIMing

Wed, 20 Aug 2008 00:00:00 GMT

The fruit fly’s internal clock mechanism, like the human mechanism, involves the complex interaction of many genes that produce the organism’s molecular clockworks. Dr. Michael Rosbash explains how fluctuating levels of specific cellular proteins operate in a negative-feedback loop to produce a molecular timekeeping mechanism. This “negative-feedback model” has proved applicable to clocks that are present in nearly every organism studied to date, from bacteria to mice and humans.

The Mammalian Timekeeper

Wed, 20 Aug 2008 00:00:00 GMT

In cloning the first mammalian clock gene, Dr. Joseph S. Takahashi and his colleagues provided clear evidence that circadian genes in mammals and fruit flies are closely related. Dr. Takahashi explains how researchers used genomics and computer-based informatics to tease out the secrets of how clocks function in higher organisms. Information about biological rhythms has far-reaching implications for human health, including gaining a better understanding of shift-work hazards, the best time to take medicines, and inherited sleep disorders such as narcolepsy.

Reading Genes and Genomes

Wed, 20 Aug 2008 00:00:00 GMT

In the 20th century, scientists deciphered the rules of inheritance, learned to manipulate DNA and sequenced the entire human genome. Dr. Eric Lander takes us on a tour of these remarkable discoveries. Studying the human genome and comparing it with the genomes of other species, in particular the mouse, offer many clues to understanding human evolution and health.

Probing Genes and Genomes

Wed, 20 Aug 2008 00:00:00 GMT

New ways of creating molecules in the lab are energizing the collaboration between chemistry and biology. Dr. Stuart Schreiber examines how technological advances in chemical synthesis and information science, coupled with data from genome projects, have made possible a research approach called chemical genetics. See how Dr. Schreiber uses chemical genetics to create small molecules that probe the functions of cellular proteins to change the way they work. These new molecules can be used to better understand how proteins work, and in some cases may become candidates for new medicines.

A Healthy Nervous System: A Delicate Balance

Wed, 20 Aug 2008 00:00:00 GMT

Mutations in key genes can lay waste to the nervous system. Spinocerebellar ataxia type 1 (SCA1), for example, can start with a stagger at age 30, eventually rendering patients unable to talk, swallow, or even breathe. Dr. Zoghbi discovered that the culprit is a sort of genetic stutter that increases the size of the SCA1 gene. As a result, the gene's protein product forms large, sticky clumps that disable the neurons involved in controlling movement. Researching compounds that will clear these tangles may also lead to treatments for other neurodegenerative diseases.

The Strength of Families: Solving Rett Syndrome

Wed, 20 Aug 2008 00:00:00 GMT

Girls with Rett syndrome develop normally for about 18 months and then begin to regress. Eventually, they have difficulty walking, speaking, and using their hands. With the help of affected girls and their families, Dr. Zoghbi and her collaborators found the gene responsible for this neurological disorder. The gene, called MECP2, encodes a protein essential to the normal functioning of nerve cells in the brain. Dr. Zoghbi discusses how identification of this gene should lead to better methods for diagnosing and treating Rett syndrome.

Human Genomics: A New Guide for Medicine

Wed, 20 Aug 2008 00:00:00 GMT

How different are two human beings from each other? Dr. Eric Lander explores human genetic variation, explaining how an understanding of small variations in DNA in individuals can help solve the mysteries of certain human diseases. Dr. Lander demonstrates an exciting new tool—the DNA microarray—that can be used to improve cancer diagnosis and treatment, and potentially increase our understanding of complex diseases.

Chemical Genomics: New Tools for Medicine

Wed, 20 Aug 2008 00:00:00 GMT

Scientists can create and test millions of new molecules to identify those useful for studying biology and new medicines. Designing and screening new molecules demands powerful information systems to keep track of all the data generated. Dr. Stuart Schreiber describes ChemBank, a new project designed to gather information that links proteins, small molecules and the functions that they affect in organisms. He suggests that in the future a synergy of chemistry, biology and computational science will help scientists view biological systems in a way that may lead to a new era of medicine.

AIDS and the HIV Life Cycle

Mon, 07 Apr 2008 00:00:00 GMT

See how far our understanding of AIDS has come since the first cases were diagnosed. What causes the immune system to become susceptible to this virus, and how are researchers building on this knowledge to improve drug treatment?

Vaccines and HIV Evolution

Mon, 07 Apr 2008 00:00:00 GMT

Despite decades of research, scientists have not closed in on developing a much-needed vaccine for HIV. A key challenge is how to address the rapid evolution of the virus within individuals, which makes if difficult to pinpoint a stable protein sequence for vaccine development.

From Outbreak to Epidemic

Mon, 07 Apr 2008 00:00:00 GMT

In 1981, homosexual men began arriving at U.S. clinics with rare cancers and infections, spurring public anxiety about the mysterious illness that would one day be known as AIDS. See how the medical community worked with sectors in public health, science and advocacy groups to mobilize in response to the deadly epidemic.

Drugs and HIV Evolution

Mon, 07 Apr 2008 00:00:00 GMT

Standard treatment for HIV with single-drug therapy changed in 1996, when a new class of antiretroviral drugs was approved. The resulting "highly active antiretroviral therapy" combines a powerful drug cocktail that causes greater disruption to the HIV life cycle and has lowered AIDS deaths in developed nations.

From Venoms to Drugs

Wed, 14 Apr 2010 00:00:00 GMT

Who knew that a snail could pack a more poisonous punch than a snake? Dr. Baldomero M. Olivera, professor of biology at the University of Utah, unveils the potency and potential of marine cone snails and their venom. While deadly to humans in its normal form, he explains how its specific toxins have been developed into a painkiller called Prialt in this video from the Howard Hughes Medical Institute.

Shedding Light on an Invisible World

Wed, 14 Apr 2010 00:00:00 GMT

Bioluminescence, or the production and emission of light by a living organism, tells scientists much about an organism’s communication system. Dr. Bonnie L. Bassler, professor of molecular biology at Princeton University, explores how quorum sensing translates to gene expression and light in this video from the Howard Hughes Medical Institute.

Biodiversity at a Snail's Pace

Wed, 14 Apr 2010 00:00:00 GMT

Cone snail venom attacks the nervous system with a mixture of peptide toxins to cause convulsive shock, sedation and even paralysis. But for scientists like Dr. Baldomero M. Olivera of the University of Utah and Howard Hughes Medical Institute, the venom also holds enormous pharmacological value. He explores the evolutionary diversity of such toxins and their potential healing properties.

Eavesdropping on Tiny Conspiracies

Wed, 14 Apr 2010 00:00:00 GMT

How do bacteria communicate across populations of millions? Quorum sensing, explains professor Bonnie L. Bassler of Princeton University and the Howard Hughes Medical Institute, allows bacteria to obtain information about their community and coordinate attacks against pathogens. The same mechanism might be used in antibiotics and is a promising new approach to drug therapy.

Mapping Memory in the Brain

Fri, 22 May 2009 00:00:00 GMT

Eric R. Kandel, Howard Hughes Medical Institute investigator, probes into the mind to demonstrate how it is much more complex than just a series of processes carried out by the brain. The brain produces our every emotional, intellectual and athletic act. It allows us to acquire new facts and skills, and to remember them for as long as a lifetime. Memory exists in two major forms, each located in different brain regions. Explicit memory is for people, places, and objects. In contrast, implicit memory serves perceptual and motor skills. In concert, these two memory systems help make us who we are.

Building Brains: The Molecular Logic of Neural Circuits

Fri, 22 May 2009 00:00:00 GMT

Thomas M. Jessel, Howard Hughes Medical Institute Investigator, explores the human brain, the sophisticated product of 500 million years of vertebrate evolution, assembled during just nine months of embryonic development. The functions encoded by its trillion nerve cells direct all human behavior. Yet the brain is a biological organ made from the same building blocks as skin, liver and lung. How does the brain acquire its remarkable computational power? Answers lie in the details of its construction -- the cellular and molecular mechanisms that drive the formation of thousands of neural circuits, each wired for a specific behavior.

Plan of Action: How the Spinal Cord Controls Movement

Fri, 22 May 2009 00:00:00 GMT

Thomas M. Jessell, Howard Hughes Medical Institute Investigator, examines the neural circuits that control our movements. Neural circuits give us a glimpse of how brain wiring and circuit activity control specific behaviors, including the movement of our limbs. Consider baseball player Lou Gehrig's remarkable hand-eye coordination, or the purity of cellist Jacqueline du Pré's tone. Yet, both examples also remind us of the fragility of the motor system: Gehrig succumbed to amyotrophic lateral sclerosis and du Pré to multiple sclerosis. Neural circuits, sensory feedback systems and signals from the brain permit us to change motor strategies to accommodate to an ever-changing world.

Memories are Made of This

Fri, 22 May 2009 00:00:00 GMT

Eric R. Kandel, Howard Hughes Medical Institute Investigator, examines whether the brain's two major memory systems, implicit and explicit, have any common features. Implicit and explicit memory both have a short-term component lasting minutes, such as remembering the telephone number you just looked up, and a long-term component that lasts days, weeks, or a lifetime, such as remembering your mother's birthday. Short-term memory is mediated by modifications of existing proteins, leading to temporary changes in the strength of communication between nerve cells. In contrast, long-term memory involves alterations of gene expression, synthesis of new proteins and growth of new synaptic connections.

Adult Stem Cells and Regeneration

Wed, 10 Sep 2008 00:00:00 GMT

Mature organisms have stem cells of various sorts, called adult stem cells. Adult stem cells are an essential source of cells for healing and regeneration in response to injury. Some animals, such as sea stars, newts, and flatworms, are capable of dramatic feats of regeneration, producing replacement limbs, eyes, or most of a body. It is an evolutionary puzzle why mammals have more limited powers of regeneration. Researchers are interested in pinpointing where adult stem cells reside and in understanding how flexible adult stem cells are in their ability to produce divergent cells such as muscle and red blood cells.

Coaxing Embryonic Stem Cells

Wed, 10 Sep 2008 00:00:00 GMT

Significant progress has been made in producing stem cell lines that, for example, participate in the regeneration of damaged nervous tissue. Many human diseases, such as juvenile diabetes (type 1 diabetes), involve malfunctioning genes and environmental triggers. Researchers want to coax embryonic stem cells into becoming healthy insulin-producing cells. These cells might then be transplanted into people with diabetes to produce the insulin they lack. Researchers are also interested in producing stem cells that malfunction exactly like the diseased cells in order to understand fundamental aspects of the disease and also to test treatments.

Stem Cells and the End of Aging

Wed, 10 Sep 2008 00:00:00 GMT

Human tissues vary in their ability to heal and regenerate. The nervous system has weak powers of regeneration, while the skin is quick to make new cells for repair. The heart is the most important muscle in the body and yet has feeble regenerative capabilities. Recent discoveries concerning the location and characteristics of adult stem cells have increased our understanding of regeneration. Insulin-like growth factor 1 (IGF1) is an example of an important stem cell communication molecule. If the activity of the growth factor is experimentally enhanced, muscle regeneration improves.