HHMI's Holiday Lectures on Science
Summary: HHMI's Holiday Lectures on Science The Howard Hughes Medical Institute is a philanthropy that supports biomedical research and science education. As part of its mission to strengthen science education, the Institute presents the Holiday Lectures on Science, an annual series that brings the latest developments in a rapidly moving field of research into the classroom. These lectures are videotaped and technical, but even the lay person can learn from them. Audio files are available, but you do lose the visual aids. However, they are still useable. Previous subjects have included, dengue, RNA, and the idea of quorum sensing which is how bacteria decide when to attack, or fireflies coordinate their flashing sequence.
With bacteria invading our best weapons, where do we begin to search for new weapons? Dr. Finlay showcases three types of bacteria--E. coli, Salmonella, and Listeria--to illustrate how molecular biology is allowing researchers to probe the molecular workings of bacterial infections. He describes how these pathogens use their genetic "toolkits" of virulence factors to cause disease. These factors, as diverse as the hosts they invade, can be transferred between different bacteria by genetic exchange, giving rise to new bacterial pathogens and diseases. Dr. Finlay discusses how an understanding of the role of virulence factors is causing disease can lead to potential new therapies for treatment and prevention.
Dr. Ganem analyses the complex causes of epidemics. He explains how both genetic mutations and changes in the environment and in human social behavior can give rise to new infectious diseases by upsetting a previously established balance between a pathogen and its natural host. He discusses how genetic changes in the structure of the influenza virus have led to epidemics and pandemics. Dr Ganem also shows the impact of weather on a 1993 outbreak of hantavirus, describes the effect of human migratory patterns on the spread of smallpox, and examines what happened when the myxoma virus was introduced in Australia in the 1950s to control the rabbit population.
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. Most, however, occur after birth, triggered by cancer-causing agents in the environment or by mistakes that happen when cells divide. If the growth of cancer can be likened to a car speeding out of control, the mutations that cause the disease are the functional equivalent of cutting the brakes, gluing down the accelerator, or hiring an inept mechanic--or doing all three at once. Dr. Vogelstein explains that although there are numerous kinds of cancer, all stem from alterations that allow cell division to outstrip cell demise.
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 anticancer therapies that take advantage of the molecular differences between cancer cells and the normal cells surrounding them. Gleevec, for example, is a compound designed to disable a protein that spurs the growth of certain types of leukemia. In Dr. Vogelstein's lab, scientists are deploying specialized microbes to penetrate tumors, proliferate rapidly, and kill the cancer cells.
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 or 40. Patients eventually experience severe muscle deterioration, rendering them unable to talk, swallow, or even breathe. By studying large families predisposed to developing SCA1, Dr. Zoghbi and her colleagues identified the responsible altered gene. The culprit is a sort of genetic stutter that increases the size of the SCA1 gene. As a result, the product of the mutant gene--a protein called ataxin-1--forms large, sticky clumps that disable the neurons involved in controlling movement. Dr. Zoghbi is now searching for compounds that will clear ataxin-1 tangles.
Girls with Rett syndrome develop normally for about 18 months and then begin to regress. Eventually, they have difficulty walking, speaking, and even using their hands. With the help of affected girls and their families, Dr. Zoghbi and her collaborators searched for the gene responsible for this neurological disorder. After 16 years, they found the gene, called MECP2, on the X chromosome. It encodes a protein essential to the normal functioning of nerve cells in the brain. Mutations in the gene disrupt the activity of neurons early in life, when they are forming critical connections. Dr. Zoghbi discusses how identification of this gene should lead to better methods for diagnosing and treating Rett syndrome.
Genetic research benefits health, but also raises thorny ethical issues. View a discussion among high school students, moderated by Huda Zoghbi and Bert Volgelstein, and ethicist Laurie Zoloth.
The 20th century opened with the rediscovery of Gregor Mendel's work on inheritance. By the close of the century, the human genome was almost fully sequenced. Dr. Lander takes us on a tour of this remarkable genetic century, demonstrating how rapid advances in DNA sequencing technologies and information science have been essential in accelerating the pace of whole-genome sequencing of different organisms. He also discusses the total number of human genes and other features of the human genome. A comparison of the human genome with the recently completed mouse genome reveals remarkable similarities, as well as some important evolutionary differences.
To understand life's processes, perturb them. How a process responds to an insult can provide clues about normal function or mimic a specific disease state. Gene mutation is one powerful perturbation method. Dr. Schreiber discusses a newer approach, called chemical genetics, that uses small molecules to bypass genes and perturb proteins directly. He illustrates the approach with the small molecule furrowstatin, which interrupts the process of cell division. Dr. Schreiber also explains diversity-oriented synthesis, a process that can rapidly create thousands of different molecules. He discusses the molecular screening methods needed to identify which of thousands of molecules may be useful for understanding a protein's function—or even for developing a new medicine.
With the exception of identical twins, no two human genomes are exactly the same. But how different are they? Are two humans more alike than two orangutans? Dr. Lander explores human genetic variation and how it may affect individual susceptibility to certain diseases. A collaborative research effort is now cataloging all common human genetic variations to help us better understand disease mechanisms. Dr. Lander also discusses a powerful tool—the DNA microarray—that can be used to measure the expression level of many genes simultaneously. DNA microarrays, for example, have been helpful in diagnosing different tumors. The widespread use of microarray technology promises to guide research into specific genes and proteins associated with many diseases.
Scientists now have the ability to create millions of new molecules. How do they test whether any of these molecules are useful? Focusing on a network of proteins involved in glucose sensing and type II diabetes, Dr. Schreiber explains two methods for screening small molecules. Small-molecule microarrays are used to screen for molecules that bind to specific proteins. In cell-based screening, proteins can be probed while performing their cellular jobs. Robotic automation and inexpensive computing have made these mass-scale parallel assays practical. Dr. Schreiber also discusses ChemBank, a project designed to gather information linking proteins, small molecules, and functions. He suggests that in the future, a synergy of chemistry, biology, and computational science may help scientists classify a host of small molecules that affect specific biological functions.
A wide-ranging 45-minute discussion between Dr. Eric Lander, Dr. Stuart Schreiber, and four Washington DC-area high school teachers, who ask the lecturers about how they became involved in science, the increasing importance of genomics in biological research, and the role of science in the classroom. Moderated by Dr. Thomas Cech, president of the Howard Hughes Medical Institute.
During embryonic development, stem cells generate all the specialized cells that populate body tissues such as muscle, the nervous system, and blood. The term embryonic stem cells, or ES cells, is used by researchers for cells that can be isolated from early embryos, before they differentiate into specific types of cells. Depending on when they are isolated, embryonic stem cells are pluripotent-able to become virtually any type of cell–or multipotent–able to become many, but not all, types of cells. Because stem cells have the potential to generate fresh, healthy cells of nearly any type, there is interest in exploring their use to treat and cure various diseases. The societal controversy regarding human ES cells relates primarily to their derivation from very early embryos. In addition, certain stem cell lines are developed using a cloning technique called somatic cell nuclear transfer, which can generate cells that are an exact genetic match to a patient.
Mature organisms have stem cells of various sorts, called adult stem cells. Adult stem cells supply cells that compensate for the loss of cells from normal cell death and turnover, such as the ever-dying cells of our skin, our blood, and the lining of our gut. They are also 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. Understanding the sources and the rules for the differentiation of adult stem cells is essential for tapping their therapeutic potential. Since consenting adults can provide adult stem cells, some people think that adult stem cells may be a less controversial area of research than embryonic stem cells.
There are two main approaches to using stem cells to fight human diseases: develop stem cells to produce therapeutic replacement cells and study stem cells as a model for understanding the biology of a disease. 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. Usually, a specific type of cell is primarily affected by the disease, and the cellular dysfunction produces the symptoms. In juvenile diabetes, the insulin-producing islet cells of the pancreas are destroyed. Insulin is critical to the proper regulation of sugar by the body, and its absence causes the severe condition called diabetes. 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.