Biotechwiz

Scientists at Liverpool, University of Bristol and the John Innes centre have released the draft sequence of the entire wheat genome. They were working in collaboration with the International Wheat Genome Consortium. This research has been funded by the Biotechnology and Biological Sciences Research Council. The work was carried out at the University’s Centre for Genomic Research, which is home to 5 next generation analyzers that can read sequences 100 times faster than those used to sequence the human genome!

This work has been received with great excitement and is expected to help wheat breeders to be able to select for strains of Wheat having desired characteristics. The reference variety used for the sequencing is the Chinese Spring Wheat (Triticum aestivum L. cv Chinese Spring) Strain. The availability of this sequence is expected to highlight natural Genetic variants between wheat types to help breeding programs. Wheat breeders have had precious little genetic information in the past to be able to make a choice as to the variety of wheat to be selected.

Wheat: One of the most important Food Crops in the World

The sheer size of the wheat genome has been daunting in terms of whole genome sequencing. The Wheat genome is about five times the size of the human genome and hence was considered close to impossible to sequence. In Comparison to other important crop plants such as Soyabean and Rice, the difficulty of working with such a large genome has left wheat lagging behind in the race of genome sequencing. However, using advanced sequencing techniques employed by Roche’s 454 sequencers, the effort has managed to cover about 95% of the known wheat genes. The results of the study are now available for public use via Genbank, EMBL and CerealsDB. Nevertheless, there are those who warn that the gene map is far from complete and that the first high quality complete map data will be available only within five years. The full sequenced genome requires further read-throughs, assembly of the data into chromosomes and significant work to fully annotate the sequence data.

According to Dr. Neil Hall of the University of Bristol, within the next 40 years the food production should be increased by at 50 % of the current value. This can only be achieved if we are able to produce wheat strains resistant to drought conditions, pesticides and salinity. Traditional methods require time consuming crosses and painstaking selection of desired characteristics sometimes after several generations. The use of genetic techniques would hopefully reduce the time frame and enable the breeder to efficiently select desired traits. These traits may include disease resistance, the ability to grow under extremes of whether and soil characteristics, & producing increased yields with minimum inputs in terms of fertilizers and other growth factors.

Wheat is one of the most important food crops around the world (though most of the wheat produces is what is known as red wheat and not the one that has been used for the study) with an estimated annual production close to 550 million tonnes. Mike Bevan of the John Innes institute has placed emphasis on the importance of the study in the light of a sharp spike in the international prices of wheat following a ban on wheat exports by Russia (due to droughts and wildfires) and the overall decrease in wheat production by countries such as Pakistan and China due to heavy rains and floods.

The wheat genome holds secrets aplenty waiting to be unlocked. We are racing against time as far as food security is concerned and any step forward is all for the best. We are waiting eagerly for the promise to be fulfilled and for the time when wheat breeders can easily and quickly select varieties that will pave the way for the next revolution. Countries like India that are struggling to meet the demands of burgeoning populations and where cultivable land is at a premium are sure to benefit from this research.

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Stem cell therapy has drawn a lot of interest lately. This therapy has shown promise in treatments of a large number of life- threatening and/or debilitating disorders that are genetic in nature. Stem cells are like base cells. They are like clay that can be molded into any desired shape. These master cells are multi potent and if given optimum conditions, they can be induced to grow into any one of the various  types of differentiated cells in our body; for example Brain or liver cells. Thus these special cells have two important attributes: 1. They can renew themselves by cell division even after relatively long periods of inaction. 2. Once they have divided, each daughter cell can either remain as a stem cell, retaining all its pluripotency or it can differentiate into any one of the different organ types in the body. Stem cells also exist in various tissue systems to serve repair functions.

Typically stem cells are divided into adult stem cells and embryonic stem cells. Embryonic stem cells are derived from the Blastocyst stage of Embryos. Embryonic stem cells can generally give rise to almost all the different cell types in the human body. Adult stem cells on the other hand, generally give rise only to all the different cells of the particular tissue from which they are derived. What does this mean? In simple terms, Hematopoetic Stem cells derived from bone marrow can give rise to all the different types of blood cells but not to cells of a very different organ system such as neurons of the brain. So in a sense they are of limited capacity. In 2006, researchers made another breakthrough by identifying conditions that would allow some specialized adult cells to be “reprogrammed” genetically to assume a stem cell-like state. This new type of stem cell is called induced pluripotent stem cells (iPSCs).

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Well, while we are on the subject of transgenics, the current news byte seems to be right on target. The latest in transgenic technology also represents a break-through in the development of animal models for testing of viral diseases. Scientists at the Salk institute in La Jola have managed to develop a mouse that has a human liver. This research was carried out principally by Dr. Inder Verma.What this means is, that the animal now sports a liver that is made up almost entirely of human hepatocytes. This will make it easier to use this mouse as a model to study human viruses affecting the liver such as Hepatitis B and C.

THe Humanised Mouse !

The problem with viruses is their host specificity. What this simply means is, viruses attacking a human being will generally have no effect on a mouse and vice versa. While this is good as the non- human viruses will not spread rapidly and infect humans, it does present substantial problems to scientists trying to study the pathology of human viruses and developing vaccines and drugs for the same. Since one cannot test therapies directly on human beings, a viable alternative needs to be provided. In the past, we have experimented with using in vitro cell cultures; liver cells grown in a Petri dish. However, this model has severe limitations due to the lack of proper organ structure and complete absence of the kind of interactions between cells and organs seen in a complete organism. Alternatives to this were to use animals such as mice that completely lacked a viable immune system (nude mice) for studying tumors of human origin. The tumors would be transplanted into these mice and their effects and probable curative measure would be studied.

However, this model has its side effects too. As Dr. Inder says, clinically speaking, a tumor does not start by acquiring millions of tumor cells from outside the system. It starts with one or two or ten cells that have lost control of their cell division cycle and hence keep on multiplying uncontrollably to give rise to a tumor. So, to that extent, transplanting a tumor into a mouse is really a fundamentally different process and may not yield real-time data as needed. However, with this new model where the mouse liver cells are literally taken over by human liver cells (Hepatocytes) so that they overgrow to give a liver that is almost entirely human, we will be able to study the actual process of tumorigenesis or viral infections along with the possible cures and vaccination methods.

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Drew Endy

Drew Endy is a forty- something Engineer. He has earned degrees in Civil, Environmental and Biochemical Engineering and today he is a faculty of the prestigious Stanford University. So, what else is new?  one might ask. Well, what is new is that his passion for building things is not limited to the sterile world of machines and electronic parts alone. Drew Andy wants to get down and dirty with Biology! “I build things, that’s what I do”, says this self- effacing man who has become the face of one of the newest kids on the technology block; Synthetic Biology. And what is this Synthetic Biology?

Wikipedia defines Synthetic Biology as follows: Synthetic biology is a new area of biological research that combines science and engineering in order to design and build (”synthesize”) novel biological functions and systems. A more technical definition states, “Synthetic biology refers to both:

• The design and fabrication of biological components and systems that do not already exist in the natural world  &,
• The re-design and fabrication of existing biological systems”.¹

To make matters simple, Synthetic Biology aims to use the components of nature as building blocks to build hitherto non-existent systems. So, how is this approach supposed to be different from the current field of Genetic Engineering? Well, in the latter, scientists cut and chop pieces of DNA, the fundamental molecule of information in living systems, from different organisms and paste them together. The aim of this is to improve the existing system by augmentation with a desirable trait from another DNA molecule. So, we have the easily cultivable E. coli cell spliced with genes producing Human Insulin yielding virtual factories of this much-needed molecule. Or we have crop plants spliced with genes to increase their tolerance to salt or to improve their yield or size of the grain, all efforts to improve the existing quality of the plant.

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We have all heard of stem cells. These are the magical ‘starter cells’ that have the capacity to grow into any type of differentiated cell of the adult body. If given optimal growth conditions and with some amount of external hormonal supplementation, theoretically one can induce these multi-potent cells to grow into say liver cells, or brain cells for that matter.

The discovery of this unique potential of these cells led to the probability of using them for therapy. What If these stem cells could be harvested and grown externally in a medium and then transplanted into patients having a chronic dysfunction of cells or organs systems? This would indeed be a much-needed breakthrough in the field of therapeutics. Thus was born the idea of Stem Cell Therapy. The process of injecting stem cells into a person or organism to repair specific tissues or to grow organs is known as Stem Cell Therapy.

Over the years Stem cell research has progressed significantly and the latest news in this field stands testimony to the hard work and relentless research of scientists working in this field. The ReNeuron Group on the second of February, 2010, announced that the UK Gene Therapy Advisory Committee (GTAC) has given a “full and final Favorable Opinion to ReNeuron’s proposed first-in-man clinical trial with its ReN001 stem cell therapy for stroke.”  The GTAC is the national research ethics committee for gene therapy and stem cell therapy clinical trials in the UK. The ReNeuron Company is a Guildford (UK) based stem cell research company. This approval represents the final stage in a long process the company has been going to through to gain approval to test its expanded neural stem cell line on patients suffering from Ischemic stroke. In the official website, the company makes the following declaration:  ‘We have received regulatory and conditional ethical approvals to commence a ground-breaking Phase I clinical trial in the UK with our lead ReN001 stem cell therapy for disabled stroke patients. We are developing stem cell therapies for a number of other conditions, including peripheral arterial disease and diseases of the retina.’ continue reading…

From the time Gautheret worked with encouraging results in the young field of PTC in 1934 and the problem of tissue culture of plant cells was definitely solved in 1939, independently by Gautheret, Nobécourt and White, the field has come a long way. With more than ten thousand researchers actively engaged in this field of research¹ the technique has undergone massive changes in method and application. From the more academic applications of trying to demonstrate totipotency and wound healing effects to generation of entirely new plants with the view to transplanting them in fields, we have witnessed the growth of an important tool of biotechnology.

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The detection and cure of cancer has become increasingly essential as a large number of people continue to succumb annually to this deadly disease. Treatment in the case of cancers poses a unique problem in terms of the high potential toxicity of many of the drugs currently being used in cancer therapy. Additionally, the fact that any method of killing cancerous cells also inevitably causes harm to normal, healthy cells and tissues further complicates the situation. Thus researchers have to find answers to some very crucial questions: First, can they reduce the effective dosage of the drug in question in order to reduce the magnitude of the damage to unwanted tissues? And second, can they control the release of the drug and or localize the drug to a specific set of cells within a tumour or in areas near it, thus preventing tissue damage? These are tough problems to tackle, especially when working with a complex system such as the human body. There is a limit to which one can reduce dosage, since one has to allow for loss of the drug through physiological processes within the body. Too low a dose might end up not really being efficacious. Localization however will end up solving both problems. If the drug can be localised, even relatively smaller doses can prove to be more efficient.

It was when I pondering over these problems that I came across some research carried out in the field of nanotechnology that was concerned with precisely the same problems. Researchers have come very close to solving the problem of localized and metered dosing of a drug within the body. This feat has been achieved by using gold nanocages. These cages are coated with a special type of “smart polymer” which can be induced to open or close using an external signal such as exposure to near-infrared light. These smart polymers are very apt for use in timed release of drugs.

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I recently read a press- release that very attractively used the term fly-paper to describe a novel invention by researchers at UCLA that can be used to grab maverick cancer cells circulating in the blood stream. These ‘mavericks’ I might add are known in Cancer jargon as Circulating Tumour Cells or CTCs. These tumour cells escape from an already formed tumour in the body and begin to circulate in the body via the bloodstream that involuntarily acts as a transport medium for these dangerous cells. The CTCs now form newer tumours in locations distinct from that of the original tumour, resulting in formation of ‘satellite tumours’ or colonies of tumour cells, giving rise to one of the most Distinctive and scaring features of a malignant tumour, namely, Metastasis.

A Cirulating Tumor Cell

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Peptide Nucleic Acid

What is a Peptide Nucleic Acid? The name is self suggestive. One can easily deduce that the molecule must be a combination of a peptide and a nucleic acid.Well, for all practical purposes that is exactly what it is. A Peptide Nucleic Acid or a PNA is a synthetic molecule that is a nucleic acid analogue or a structural mimic. A natural nucleic acid (DNA or RNA) has a sugar phosphate backbone linking together the nucleotide bases. In a PNA, the nucleotides are retained, but the charged Sugar phosphate bridges are replaced with a synthetic peptide backbone that is usually composed of N-(2-amin-ethyl)-glycine units. This modification yields an uncharged and a chiral molecule, which follows the rules of the Watson and Crick base pairing as faithfully as its Nucleic acid cousin. In addition, PNA now becomes resistant to enzymatic degradation and exhibits increased thermal and ionic tolerance. Now, the PNA due to its unique structural features can recognise DNA and RNA in a sequence-specific manner. Also what is most interesting is that it recognises duplex DNA, and binds to it by strand invasion forming a triplex PNA-DNA-PNA.This form is extremely stable. Any student of Biotechnology would have by now grasped the immense significance of this molecule with respect to its Pharmacological and Diagnostic abilities. It is the tremendous versatility and the potential of this molecule that brings it into focus in this week’s Cutting Edge.

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