Saturday, November 16, 2013

Research findings call for a rethinking of cancer genetics

Johns Hopkins researchers report that the deletion of any single gene in yeast cells puts pressure on the organism’s genome to compensate, leading to a mutation in another gene. Their discovery, which is likely applicable to human genetics because of the wayDNA is conserved across species, could have significant consequences for the way genetic analysis is done in cancer and other areas of research, they say.
Deletion of Gene B causes instability in the 
genome that is compensated for through a 
secondary mutation in Gene A. 
Credit: Xinchen Teng
Summarized in a report to be published on Nov. 21 in the journal Molecular Cell, the team's results add new evidence that genomes, the sum total of species' genes, are like supremely intricate machines, in that the removal of a single, tiny part stresses the whole mechanism and might cause another part to warp elsewhere to fill in for the missing part.
"The deletion of any given gene usually results in one, or sometimes two, specific genes being 'warped' in response," says J. Marie Hardwick, Ph.D., the David Bodian Professor of Molecular Microbiology and Immunology at the Johns Hopkins Bloomberg School of Public Health and a professor of pharmacology and molecular sciences at the school of medicine. "Pairing the originally deleted gene with the gene that was secondarily mutated gave us a list of gene interactions that were largely unknown before."
Hardwick says the findings call researchers to greater scrutiny in their genetic analyses because they could unwittingly attribute a phenomenon to a gene they mutated, when it is actually due to a secondary mutation.
“This work has the potential to transform the field of cancer genetics,” Hardwick says. “We had been thinking of cancer as progressing from an initial mutation in a tumor-suppressor gene, followed by additional mutations that help the cancer thrive. Our work provides hard evidence that a single one of those ‘additional mutations’ might come first and actively provoke the mutations seen in tumor-suppressor genes. We hope that our findings in yeast will help to identify these ‘first’ mutations in tumors.”
The beauty of working with yeast, Hardwick says, is that it is easy to delete, or "knock out," any given gene. Her team started with a readily available collection of thousands of different yeast strains, each with a different gene knockout.
At their preferred temperature, each of these strains of yeast grows robustly even though they each have a different gene missing. Hardwick's team first asked a fundamental question: Within a given strain of yeast, does each cell have the same genetic sequence as the other cells, as had generally been presumed?
"We know, for example, that within a given tumor, different cells have different mutations or versions of a gene," explains Hardwick. "So it seemed plausible that other cell populations would exhibit a similar genetic diversity."
To test this idea, her team randomly chose 250 single-knockout strains from the thousands of strains in the collection. For each strain, they generated six sub-strains, each derived from a single yeast cell from the “parental batch.”

They then put each sub-strain through a "stress test” designed to detect sub-strains with behaviors that varied from the behavior of the parental batch. All of the sub-strains grew indistinguishably without stress, but when the temperature was gradually raised for only a few minutes, some sub-strains died because they could not handle the stress. When the Hardwick team examined their genes, they found that, in addition to the originally knocked-out gene, each of the sub-strains that faltered also had a mutation in another gene, leading the team to conclude that the cells in each strain of the single-gene knockouts do not all share the same genetic sequence.
They then tested all 5,000 of the original single-gene knockout strains to find sub-strains that could overgrow when given low-nutrient food — a trait that tumor cells often possess. This was another stress test designed to detect differences between the individual cells taken from the parental batches. They identified 749 such knockout strains and showed that their growth differences were often due to secondary mutations.
In total, the team’s evidence indicates that 77 percent of all the knockout strains have acquired one or two additional mutations that affect cell survival and/or excessive growth when food is scarce.
Hardwick believes that stressing yeast in other ways may lead to an even higher percentage of double-mutant strains. In fact, she said she believes that “essentially any gene, when mutated, has the power to alter other genes in the genome." Deleting the first gene seems to cause a biological imbalance that is sufficient to provoke additional adaptive genetic changes, she explains.
Furthermore, in all of the strains that they examined, they found that the secondary mutations that appeared after a given knockout were always in the same one or two genes as in their earlier observations. Unexpectedly, Hardwick said, the altered growth of the sub-strains was usually due to the secondary mutations, not the original knockout, and many of those secondary mutations were in genes that are known to becancer-causing in humans.

Description, Areas and Scope of Medical Microbiologist

Description, Areas and Scope of Medical Microbiologist

Medical microbiology course is branch within the field of medicine which focuses on micro organisms of medical interest which include the bacteria, viruses, fungi and parasites which are of medical importance and are capable of causing infectious diseases in human beings. Microbiologists can rather be called as detectives who investigate in the microscopic world - a world that holds much wonder and mystery, the world which much people cannot see.

Medical Microbiology Course description includes the study of microbial pathogenesis and epidemiology and is related to the study of disease pathology and immunology. Microbiologists study micro organisms which can cause disease in people, looking into life cycles of such organisms, on how they cause infection, how they spread, and cause disease, the means to treat the diseases and irradiate the disease causing microbes.

This field of microbiology is constantly engaged with identifying new micro organisms, monitoring changes in rapidly mutating species and dealing with the ongoing challenges in medicine, ranging from the development of resistance to antibiotics in bacteria to contamination of water supplies with protozoans. They work in all ways to contribute to mankind and improve humans and environmental quality of life and living.

SCOPE AND CAREER PROSPECTS FOR A MICROBIOLOGIST:

TEACHING : If you are interested in teaching as a profession and if you are interested to pursue your masters degree, and you are basically a science student, then microbiology is the best suited to pursue a masters in. Teaching is a noble profession, and the returns after completing your study is tremendous. And again the scope is vast as it is the basic subject of study in all medical colleges as well as Para medical colleges like dental science, physiotherapy, pharmaceutical science, nursing science, radiography, lab technology etc. It is the most highly paid among the teaching profession in science, even at the initial stage as a beginner. As well you get an opportunity to work among the dignified doctors and amongst the highly esteemed medical professionals. Academic microbiologists are employed by universities, schools and teaching hospitals.
RESEARCH SCIENTIST : Research is a never ending field and thus one can take up research. As a research scientist a microbiologist can work in universities, institutions, industries, hospitals, government organizations and carry out research in laboratories. Many work as associate or assistant scientists or researchers doing the routine work of conducting experiments, others are senior scientists or project managers who lead experiments, supervise lab workers, interpret data and develop new theories and experiments.
CLINICAL ASSOCIATE : One can get into clinical research as clinical coordinator or clinical trials administrator and later on generally qualify to move on to a full clinical research associate position.CLINICAL MICROBIOLOGIST - Clinical microbiologist assist the treating team of doctors with the investigations, diagnosis and treatment of disease. That analyze and interpret data related to patient samples. They work for the betterment of the society by engaging in a wider range for complex work in laboratories specially against incurable, life threatening diseases like cancer, AIDS etc. They advise clinicians on the use of tests, diagnosis of disease and planning and progress of the treatment. They work to combat problems such as outbreaks of epidemics, food poisoning, pollution of air and water, for eg., they check blood samples sent in by physicians to check for any communicable diseases.
TOXICOLOGIST : Microbiologists are employed as toxicologists in investigatory laboratories. They plan and carry out laboratory and field studies to identify, monitor and evaluate the impact of toxic materials and radiations on human and animal health, and on the health and current status of the environment, as well as the impact of future technologies.
FORENSIC SCIENTISTS : Microbiologists with appropriate skills are also considered for posts in forensic science.
BIOMEDICAL SCIENTISTS : Following basic training, most biomedical scientists specialize in one aspect of medical laboratory science. The main areas are microbiology, clinical chemistry,transfusion science, hematology, histopathology, cytology, immunology and virology.
BIOSTATISTICIAN : Biostatisticians are statisticians who work in th health related fields. They design research studies and collect and analyze data on problems such as how disease progress, how safe is the treatment, or the impact of certain risk factors associated with medical conditions.
Microbiologists have enough and more jobs as quality assurance specialists in the pharmaceutical companies, food processing industry, diary and milk products, beverages, hotels, biotechnology companies, agriculture, forestry etc.
Phd. : for those interested in further study, they can take up doctorate and go for further specialization and research. Foreign fellowships for doctorate degree are also available.They can also work for medical and scientific publishing firms.
LIST OF VARIOUS POST GRADUATE COURSES OFFERED IN MEDICAL MICROBIOLOGY:

B.Sc - Bachelor of science in medical microbiology
M.Sc - Masters of science in medical microbiology
M.D - Doctor of medicine in medical microbiology
Phd - Doctorate in medical microbiology