Thursday, December 27, 2012

Fermentation

Fermentation

The word fermentation is derived from a latin verb ‘fervere’ which means to boil. However, events of boiling came into existence from the fact that during alcoholic fermentation, the bubbles of gas (CO2) burst at the surface of a boiling liquid and give the warty appearance. The conventional definition of fermentation is the breakdown (metabolism) of larger molecules. For example, carbohydrates, into simple ones under the influence of micro-organism for their enzymes. This definition of fermentation had little meaning until the metabolic process were known. In a micro-biological way, fermentation is defined as “any process for the production of useful products through mass culture of micro-organism” wheteras, in a biochemical sense, this word means the numerous oxidation – reduction reactions in which organic compounds, used as source of carbon and energy, act as acceptors of donors of hydrogen ions. The organic compounds used as substrate give rise to various products of fermentation which accumulate in the growth medium (Riviere, 1977)

Almost in all organism metabolic pathways generating energy are fundamentally similar. In autophototrophs, (e.g. some bacteria, cyanobacteria and higher plants) ATP is generated as a result of photosynthesis electron transport mechanisms, whereas in chemotrophs the source of ATP is oxidation of organic compounds in the growth substrates. The oxidation reaction may be accomplished in the presence of oxygen (in aerobes) or in absence of oxygen (in anaerobes). Thus, in aerobic microorganism the process in ATP generation is referred to as cellular respiration whereas in anaerobes or aerobes functioning under anaerobic condition, it is known as anaerobic respiration or fermentation.

Although, fermentation (e.g. brewing and wine production) was done for many hundred years, yet during the end of 15th century, brewing became partially industrialized in Britain. Antony van Leeuwenhoek (1632-1723) developed method to observe yeasts and other micro-organism under the microscope but this study could not be further strengthened. By early 19th century Cagniard-Latour and Schwann reported that the fermentation of wine and beer is accomplished by yeast cells. It was L. Pasteur who observed microorganism associated with fermentation and causing many diseases in human beings. Detailed studies on fermentation products, culture improvement, recovery, and scale up of products were made after the world war I.

The Human Genome Projects - Benefits

The Human Genome Projects - Benefits

The work on interpretation of genome data is still in its initial stages. It is anticipated that detailed knowledge of the human genome will provide new avenues for advances in medicine and biotechnology. Clear practical results of the project emerged even before the work was finished. For example, a number of companies, such as Myriad Genetics started offering easy ways to administer genetic tests that can show predisposition to a variety of illnesses, including breast cancer, disorders of hemostasis, cystic fibrosis, liver diseases and many others. Also, the etiologies for cancers, Alzheimer's disease and other areas of clinical interest are considered likely to benefit from genome information and possibly may lead in the long term to significant advances in their management.
There are also many tangible benefits for biological scientists. For example, a researcher investigating a certain form of cancer may have narrowed down his search to a particular gene. By visiting the human genome database on the worldwide web, this researcher can examine what other scientists have written about this gene, including (potentially) the three-dimensional structure of its product, its function(s), its evolutionary relationships to other human genes, or to genes in mice or yeast or fruit flies, possible detrimental mutations, interactions with other genes, body tissues in which this gene is activated, diseases associated with this gene or other datatypes.Further, deeper understanding of the disease processes at the level of molecular biology may determine new therapeutic procedures. Given the established importance of DNA in molecular biology and its central role in determining the fundamental operation of cellular processes, it is likely that expanded knowledge in this area will facilitate medical advances in numerous areas of clinical interest that may not have been possible without them.The analysis of similarities between DNA sequences from different organisms is also opening new avenues in the study of the theory of evolution. In many cases, evolutionary questions can now be framed in terms of molecular biology; indeed, many major evolutionary milestones (the emergence of the ribosome and organelles, the development of embryos with body plans, the vertebrate immune system) can be related to the molecular level. Many questions about the similarities and differences between humans and our closest relatives (the primates, and indeed the other mammals) are expected to be illuminated by the data from this project.
The Human Genome Diversity Project, spin-off research aimed at mapping the DNA that varies between human ethnic groups, which was rumored to have been halted, actually did continue and to date has yielded new conclusions. In the future, HGDP could possibly expose new data in disease surveillance, human development and anthropology. HGDP could unlock secrets behind and create new strategies for managing the vulnerability of ethnic groups to certain diseases (see race in biomedicine). It could also show how human populations have adapted to these vulnerabilities.

What's Turning Genomics Vision Into Reality

In "A Vision for the Future of Genomics Research," published in the April 24, 2003 issue of the journal Nature, the National Human Genome Research Institute (NHGRI) details a myriad of research opportunities in the genome era. This backgrounder describes a few of the more visible, large-scale opportunities.

The International HapMap Project

Launched in October 2002 by NHGRI and its partners, the International HapMap Project has enlisted a worldwide consortium of scientists with the goal of producing the "next-generation" map of the human genome to speed the discovery of genes related to common illnesses such as asthma, cancer, diabetes and heart disease.Expected to take three years to complete, the "HapMap" will chart genetic variation within the human genome at an unprecedented level of precision. By comparing genetic differences among individuals and identifying those specifically associated with a condition, consortium members believe they can create a tool to help researchers detect the genetic contributions to many diseases. Whereas the Human Genome Project provided the foundation on which researchers are making dramatic genetic discoveries, the HapMap will begin building the framework to make the results of genomic research applicable to individuals.

ENCyclopedia Of DNA Elements (ENCODE)

This NHGRI-led project is designed to develop efficient ways of identifying and precisely locating all of the protein-coding genes, non-protein-coding genes and other sequence-based, functional elements contained in the human DNA sequence. Creating this monumental reference work will help scientists mine and fully utilize the human sequence, gain a deeper understanding of human biology, predict potential disease risk, and develop new strategies for the prevention and treatment of disease.The ENCODE project will begin as a pilot, in which participating research teams will work cooperatively to develop efficient, high-throughput methods for rigorously and fully analyzing a defined set of target regions comprising approximately 1 percent of the human genome. Analysis of this first 30 megabases (Mb) of human genome sequence will allow the project participants to test and compare a variety of existing and new technologies to find the functional elements in human DNA.

Chemical Genomics

NHGRI is exploring the acquisition and/or creation of publicly available libraries of organic chemical compounds, also referred to as small molecules, for use by basic scientists in their efforts to chart biological pathways. Such compounds have a number of attractive features for genome analysis, including their wide structural diversity, which mirrors the diversity of the genome; their ability in many cases to enter cells readily; and the fact that they can often serve as starting points for drug development. The use of these chemical compounds to probe gene function will complement more conventional nucleic acid approaches.This initiative offers enormous potential. However, it is a fundamentally new approach to genomics, and largely new to basic biomedical research as a whole. As a result, substantial investments in physical and human capital will be needed. NHGRI is currently planning for these needs, which will include large libraries of chemical compounds (500,000 - 1,000,000 total); capacity for robotic-enabled, high-throughput screening; and medicinal chemistry to convert compounds identified through such screening into useful biological tools.

Genomes to Life

The Department of Energy's "Genomes to Life" program focuses on single-cell organisms, or microbes. The fundamental goal is to understand the intricate details of the life processes of microbes so well that computational models can be developed to accurately describe and predict their responses to changes in their environment."Genomes to Life" aims to understand the activities of single-cell organisms on three levels: the proteins and multi-molecular machines that perform most of the cell's work; the gene regulatory networks that control these processes; and microbial associations or communities in which groups of different microbes carry out fundamental functions in nature. Once researchers understand how life functions at the microbial level, they hope to use the capabilities of these organisms to help meet many of our national challenges in energy and the environment.

Structural Genomics Consortium

Structural genomics is the systematic, high-throughput generation of the three-dimensional structure of proteins. The ultimate goal for studying the structural genomics of any organism is the complete structural description of all proteins encoded by the genome of that organism. Such three-dimensional structures will be crucial for rational drug design, for diagnosis and treatment of disease, and for advancing our understanding of basic biology. A broad collection of structures will provide valuable biological information beyond that which can be obtained from individual structures.

Monday, August 20, 2012

A Possible Cure for HIV

A Possible Cure for HIV 

 

Patients who have recently been able to clear or control their acquired immune deficiency syndrome (AIDS) have renewed the interest of scientists in finding a cure for the human immunodeficiency virus (HIV) and subsequently, AIDS. The newest ideas to help generate a cure include transplants of naturally resistant stem cells or the genetic modification of immune cells to render them immune to the virus (Pollack 2011). Since people with HIV are required to take antiviral drugs to control the infection for the rest of their lives the discovery of a cure would improve countless lives and solve one of the world’s foremost health issues.

HIV is a retrovirus which attacks the cells of the human immune system, causing their inability to function. As the HIV infection advances, the immune system of the person gradually weakens, making them more vulnerable to other illnesses. The last stage of the HIV infection, AIDS, usually takes 10-15 years to reach and antiviral drugs can slow the development down even further (World Health Organisation 2012).
In the first patient, a man seemingly cleared his HIV infection through numerous bone-marrow transplants he received as leukemia treatment. The donor was one of the 1% of Northern Europeans that lack a protein, CCR5, rendering him naturally resistant to HIV. Due to the bone-marrow (stem cell) implant the patient is able to produce a resistant immune system and has been free of the virus for four years (CBS News 2011). However, this approach for a cure is unlikely due to the difficulties of finding a matching donor as well as the transplant procedure being risky and expensive. In addition, donors would be unethically ‘farmed’ for bone-marrow. Therefore this approach for a cure is highly improbable.

Scientists attempted to modify the immune cells of the second patient, eliminating the CCR5 protein, in order to make them resistant to HIV. White blood cells were removed from the body of the patient and put through gene therapy which modified the cells to produce another protein which disrupted the CCR5 protein. The treated cells were replaced into the man’s body and a month later the man stopped taking antiviral drugs as part of the experiment. Initially, the amount of HIV rose sharply, as expected, but then dropped to an undetectable level gradually while immune cell counts rose. However, the gene therapy did not work as well in 5 other patients (Pollack 2011). This approach to a cure is unproven through these patients but is still being developed, moving onto further clinical trials earlier this year (Instinct Staff 2012). This idea presents numerous problems, the main one being that each individual would have to undergo the procedure making this cure implausible at this point.

Although there is great need of a cure for HIV, with the current methods and ideas involving stem cell transplants and gene modifications, it is doubtful that a functional cure that can be used on a wide scale will be found in the near future.

Gene Therapy Restores Vision

Gene therapy is an exciting treatment option that is starting to take off in the field of treating genetic diseases. Three women in the United States, who had previously been treated for genetic blindness with gene therapy in one eye, have been treated in the second eye, and the results are looking promising (http://www.bbc.co.uk/news/health-16942795). Gene therapy is still only in its early stages as a treatment option, but the promise of recent studies into its success in treating genetic eye diseases mean this technology is on the rise and could soon become a widespread treatment option throughout the world.

Genetic disorders are caused by the malfunctioning of one or more of our genes, which prevent the proteins in our body, which are instructed by the genes, from fulfilling their normal functions (http://www.ornl.gov/sci/techresources/Human_Genome/medicine/genetherapy.shtml). In gene therapy, the malfunctioning gene is replaced by a new, better-functioning gene, which is inserted into the area of the body where the faulty gene is located (http://www.scientificamerican.com/article.cfm?id=experts-gene-therapy). If we do not replace this malfunctioning gene, it can be the cause of disease within in the body. Gene therapy was first tested for treating genetic blindness back in 2008, when a research team at Moorfields Eye Hospital’s NIHR Biomedical Research Centre in the UK used gene therapy successfully on the eyes of human patients, proving it was safe and helped to improve their sight (http://www.ornl.gov/sci/techresources/Human_Genome/medicine/genetherapy.shtml).

In early 2012, three women in the US were treated with a second round of gene therapy to relieve their genetic blindness, caused by an inherited condition known as Leber’s Congenital Amaurosis (LCA). LCA is a very rare disease, appearing just after birth, and occurring as cells from the retina, the “light-sensitive layer of cells at the back of the eye” (Briggs 2012), progressively die out over time, degrading the vision of the sufferer. It is caused by a faulty gene in the cells of the retina, RPE65, and gene therapy aims to fix this by injecting a virus containing a functioning version of the gene into the eye. Dr Jean Bennett, of the University of Pennsylvania’s Mahoney Institute of Neurological Sciences, first treated the three women with this method back in 2008. At the time, twelve people suffering from LCA were injected in just one eye, recovering some vision in the injected eye, and in early 2012, the three women were chosen out of the twelve to have the procedure repeated in the second eye, showing a notable improvement in the vision quality in both eyes. Information regarding Dr Bennett’s most recent results in this area can be found in the February 8th edition of Science Translational Medicine (http://stm.sciencemag.org/content/4/120/120ra15.full.html 2012).

It is evident that, in the last few years, gene therapy has started to emerge as a potentially successful treatment for genetic diseases, in particular those involving genetic blindness. Recent studies, such as the ones referred to above, have demonstrated gene therapy to be successful in improving vision quality for those suffering from inherited eye diseases, such as LCA, and have provided evidence that it is a safe treatment option. It is hoped that these discoveries will lead to more widespread use of gene therapy as a valid treatment for genetic blindness, and will improve the quality of life of those suffering from poor vision quality as a result of inherited eye conditions.

Wednesday, August 15, 2012

Genetics and Bacterial Resistance


Genetics and Bacterial Resistance

Bacteria have many mechanisms for adapting to their environment and they certainly use them when responding to adverse conditions. In particular, bacteria such as Eschericha coli go through many genetic mutations when building resistance to various antibiotics (Toprak et al. 2012). A team of scientists at Harvard have developed a method for recording and understanding these mutations in an experiment which could have future implications on the way we approach bacterial infections (stealth tactics of bacteria revealed, 2012).

aims to not only record, but understand precisely how bacteria forms a resistance to antibiotics. In order to control the present antibiotic, the concentration of that drug and to record how the bacterium responds, they created the ‘morbidostat’ (stealth tactics of bacteria revealed, 2012). Results have been obtained from E. coli as it was monitored about how it responded to controlled doses of various antibiotics.



The results showed that the bacteria developed resistance to all three of the introduced antibiotics (stealth tactics of bacteria revealed, 2012). Some antibiotics can be faulted by a single gene change, although in this case, like many others, a number of genetic mutations had to occur to obtain the desired phenotype (Toprak et al. 2012). The group of genetic mutations that occurred in this case targeted the bacteria’s susceptibility to each of the antibiotics. The way in which the bacteria responded to the three test drugs separately was a testament to the variability bacteria is capable of. Achaean organisms are widely recognized for their adaptive abilities, which stem from their methods of reproduction. High generational rates are achieved by the ability of the organisms to use binary fission.  Also, plasmids play a role in increasing the genetic material available to the bacteria (Campbell et al. 2009). These mechanisms give reason for the successful rapid mutation of genes measured within the experiment.

The mutations occurring within the bacteria differed between the types of antibiotic it was exposed to (Toprak et al. 2012). The differences between these changes can be applied to the way the bacteria’s resistance developed. But perhaps the most useful data that resulted from this experiment was the congruency between separated test populations.  The genomes of bacteria responding to the same drug, which were measured throughout the test, concluded that “parallel populations evolved similar mutations and acquired them in a similar order.” (Toprak et al. 2012, p101). The patterns that were observed suggests that there are specific pathways of mutation, along which bacteria moved to achieve a goal; antibiotic resistance (Toprak et al. 2012). Now that these genetic pathways have been measured, a more complex set of knowledge can be applied to improving antibiotics and increasing their effectiveness in the future.

A greater understanding of bacteria and it’s mechanisms for coping with its environment is being achieved through many studies being conducted, genetic resistance is a particularly relevant topic and developing improved ways of treating bacterial infections in humans is highly beneficial. The measurement of the response of bacteria to antibiotics has resulted in evidence of mutational pathways for bacteria gaining resistance (Toprak et al. 2012). These results are of great significance to the notions of improving the antibiotic method and overcoming bacterial resistance.