Biotechwiz

The draft sequence of the Wheat Genome (Chinese Spring Wheat) has been released and researchers are eagerly looking forward to the possibilities of developing drought resistant, salinity resistant and pest resistant varieties of this important crop plant. Biotechwiz spoke to eminent Wheat Physiologist Dr. Matthew Reynolds from the CIMMYT (International Maize and Wheat Improvement Center) about this momentous development. Dr. Reynolds has been associated with Dr. Norman Borlaug, Nobel prize winner and agronomist whom most readers would know as ” the father of the Green Revolution” Dr. Borlaug was head of the Wheat Program at the CIMMYT.

The Interview with Dr. Reynolds is the first of two parts. The second part will be devoted exclusively to his role in the CIMMYT and the yeoman service this organization has carried out in taking the world closer to food security.

Biotechwiz presents excerpts from an exclusive interview with Dr. Matthew Reynolds, who has been intimately connected with improvement of Wheat strains, on the release of the draft sequence of the reference strain of the Chinese Spring Wheat:

Dr Matthew Reynolds: CIMMYT

Biotechwiz: You are described as a wheat physiologist. Can you elaborate on the nature of your work?

Dr. Matthew Reynolds:  As wheat physiologist at CIMMYT the main task is to uncover ways to improve the ability of wheat to be more productive in a range of the environments from those with high yield -such as the Punjab- to those with heat and drought stress, with a special focus on developing countries. Activities encompass the following broad objectives: Through wide consultation define factors that limit current productivity; Develop breeding technologies through collaborative research encompassing novel and conventional approaches; Coordinate multidisciplinary elements of projects over different target countries thereby facilitating relevance and delivery of products; Lead a team of scientists and technicians in Mexico to address specific research objectives as well as human capacity development.

BW: The draft sequence of the genome of the Chinese Spring wheat has just been released. What, according to you, will be the most immediate benefit of this work?

Dr. Reynolds: There will be no immediate benefit as the job of sequencing must be completed thoroughly, however, the long term benefits will be that we can use genetic information to more precisely move useful physiological traits into good agronomic cultivars.

BW: You have spoken in earlier articles of the need to develop crops that will be more resistant to climate change. Do you think that the draft sequence will reveal sufficient data in order to be able to develop such plants or will we need to wait for the finished sequence?

Dr. Reynolds: It will most likely need to wait for the finished sequence.

BW: Breeders have reacted to the news saying they will be able to select for specific traits such as drought or salinity resistance using ‘Macro- assisted selection’. Can you tell us how they would carry out such selection and what does macro-assisted selection actually mean?

Dr. Reynolds: I have not heard of macro-assisted selection before. I assume it refers to whole genome selection, which is a way of taking into account the diversity of the whole genome as opposed to focusing on a few loci. Certainly complex traits like drought adaptation will benefit from considering the whole genome as their genetic basis is complex.

BW: Could you tell us a bit about the CIMMYT and the role you play in the organisation? Also will your organisation be working on developing newer strains of wheat using the sequence data that has become available?

Dr. Reynolds: CIMMYT -a member of the Consultative Group on International Agricultural Research (CGIAR)- partners with hundreds of breeders worldwide and delivers new crop genotypes to developing countries on a large scale as freely available global public goods. The impact of this work on the livelihoods of resource-poor farmers in less developed countries is well documented. The value of the international wheat breeding effort coordinated by CIMMYT is estimated at several billion dollars of extra revenue annually, spread among millions of farmers. While the impact of the so called Green Revolution cultivars were initially in relatively favourable environments, subsequent breeding and dissemination effort has resulted in economic benefits in more marginal environments, including those affected by drought and heat stress. This breeding-evaluation-delivery pipeline encompasses the following elements: (i) free exchange of germplasm with national agricultural research services worldwide, (ii) a centralized breeding effort that focuses on generic needs –i.e. yield potential, yield stability, genetic resistance to range of biotic and abiotic stresses, consumer-oriented quality traits-, (iii) distribution of international nurseries targeted to a number of major wheat agro-ecosystems via national wheat programs in over 120 countries, (iv) analysis of international yield trials and global disease monitoring to ensure relevance of current local, regional and global breeding activities, (v) capacity building and training of research partners, (Reynolds and Borlaug, 2006; attached).

BW: Finally, would you like to speculate on the time-frame it is likely to take for the benefits of the sequence data to become obvious?

Dr. Reynolds: I was told it will take around 5 years to complete the project, then their will be a research phase, followed by application and breeding. Could be around 20 years before benefits are felt by farmers.

Image Credit:

http://blog.cimmyt.org/?s=mathew++reynold

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.

An Interview with Dr. Krishanu Saha from the Whitehead Institute of Biomedical Research: On the invention of a new Synthetic Surface for the Cultivation of Human Stem cells for up to three months.

Scientists at MIT have developed a novel synthetic surface for the cultivation of human stem cells. The research team, led by Professors Robert Langer, Rudolf Jaenisch and Daniel G. Anderson, describes the new material in the Aug. 22 issue of Nature Materials. First authors of the paper are postdoctoral associates Krishanu Saha and Ying Mei. The new material was singled out of almost 500 polymers designed during the course of the study, and was found to be optimal after analysing  several chemical and physical properties of surfaces, including roughness, stiffness, and affinity for water that might play a role in stem cell growth. The new surface not only enabled Stem Cells to be grown for up to three months but also enabled harvesting of cells in the millions. Both of these attributes are very important to researchers as the in vitro culture of human Stem cells is fraught with difficulty. The surface also enables clonal growth of a stem cell allowing for easy selection of a particular cell with attributes of interest. As Researchers laud this important invention, Biotechwiz is proud to present an exclusive interview with Dr. Krishanu Saha, one of the authors of this seminal work. An excerpt of the interview is presented below:

Dr. Krishanu Saha

Biotechwiz: Why did you feel the need to develop a new material for the growth of stem cells?

Dr. Krishanu Saha: When we started this work, there were only a handful of culturing materials that were used to grow human embryonic stem cells. Most of these materials included components from animal sources. These animal-derived components are problematic for any cell therapy applications envisioned with these cells, because such components utilized during cell culture can increase the risk of immune rejection when such cells are injected into a patient.  We therefore sought to explore whether a library of synthetic polymers coated with human-derived proteins could replace and improve on the conventional methods of growing human embryonic stem cells.

We also wanted to gain more molecular insight into how human embryonic stem cells grow outside of the body. Mouse embryonic stem cells have particular properties of cell growth and genetic manipulation that make them easier to work with in the lab.  We wondered whether we could devise better culture conditions for human embryonic stem cells by systematically exploring stem cell growth on a diverse set of polymeric materials.

BW: Can you elaborate a bit on the nature of this new surface that you have developed and what is the most unique feature of your invention according to you?

Dr. Saha: The new surfaces can be synthesized entirely from standard chemicals.  They utilize a particular chemistry that was not defined before this work to interact with a human protein, Vitronectin.  The most unique feature is that it can support the long-term culture of fully dissociated human embryonic stem cells as well as the recently ‘reprogrammed’ human induced pluripotent stem cells.

BW:  How soon do you think the research you have done will be available as a commercially viable product?

Dr. Saha: This question of technology transfer is a difficult one to predict. There are already a few commercial products based on other work with novel stem cell culture materials that was just published in May. So if we extrapolate from those cases, our work could be translated into products in less than a year.  I believe the MIT technology transfer office is dedicated to ensuring that the materials get widely used.

BW:  What is the trend your future research is likely to take?

Dr. Saha: I am generally interested in combining this work with recent advances in cellular reprogramming. Cellular reprogramming can produce embryonic stem cell-like cells called induced pluripotent stem (iPS) cells from virtually any human cell source, such as a blood sample or biopsy.  I believe there is a key role of materials and engineering to play in developing these iPS cells for disease modelling and regenerative medicine applications.

BW: Can you tell us about any one hurdle that bugged you the most during your work?

Dr. Saha: Finding common patterns in the material characteristics that controlled the growth of the human embryonic stem cells was challenging.  We had hundreds of polymers with lots of data about surface chemistry, stiffness, and roughness that needed to be sorted and globally analyzed. At times, this seemed tedious, but it is part of the research process.

A lot of research depends upon making comparisons between healthy and sick individuals. And the results of these comparisons have been used to develop newer and better diagnostics, prophylactics and treatments. The current study is also pretty much based on comparison between ducks that are infected with the Bird Flu virus and those that were completely healthy. The only difference here being that the comparison involved the smell of the feaces of the two groups of ducks in question, and the ‘detectors’ of these olfactory differences were lab-trained mice!

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For all those who were waiting with bated breath for the first ever Human Embryonic stem cell (HESC) phase I clinical trials to begin, well there’s good news. On the 30^th of July 2010, the US based Geron Corporation announced the FDA’s approval to its HESC based clinical trials in humans. The announcement comes after a year-long set-back to the proposed trials, after the company discovered during some of its tests that the rats treated with the stem cell line developed cysts. This set off a spate of further tests to ensure efficacy and safety of the therapy. After a year, the company seems to have effectively allayed fears of tumorigenicity and has obtained a green signal from the US FDA and will be beginning the first human trials of Human Embryonic stem cell therapy in the world.

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The District Court Judge of the Southern District of New York, Judge Robert Sweet will go down in History. Amidst much speculation and debate, the Judge, on March 29^th 2010, ruled in the case of Association for

Judge Robert Sweet

Molecular Pathology v. U.S. Patent and Trademark Office, that the patents For BRCA1 and BRCA2 held by the company Myriad Genetics, were invalid. The decision was a highly anticipated one since this particular lawsuit has been hailed by many as being a direct attack on the company and the USPTO (The United States Patent and Trademarks Office). The issue of gene patenting has always been a controversial one and there have been heated debates for and against it. However, in recent times, we have seen with increasing unease, the extent to which essential health care testing, diagnostics and even treatments have slowly but steadily passed the truly needy patients by because of prohibitively high costs and monopolistic trade practices by many such companies in the name of millions of dollars sunk into research for the same.

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DIABETES

On the third of March 2010, UK based leading stem cell Therapy Company ReNeuron announced positive pre-clinical data for the treatment of Peripheral Arterial Disease (PAD) in Diabetic Patients using its indigenously developed Stem cell line ReN009. PAD occurs when there is a build-up of plaque in the arteries. This plaque generally is made up of fats and cholesterol, calcium and fibrous components of the body. Periodic build-up of such fats in the arteries can cause them to harden and narrow the lumen (Hollow space) of the artery. This narrowing prevents proper blood flow within the body. Known as Atherosclerosis, this generally affects blood flow to the legs but can also affect flow to kidneys hands and other parts of the body. PAD is a chronic and debilitating disease that progressively restricts blood flow in the limbs, causing cramping, chronic pain and in extreme cases, amputation.  PAD is commonly associated with other conditions, including diabetes, obesity and stroke.  At least 1 in 20 people over the age of 55 have some degree of PAD and it becomes more common with increasing age. For more on this disease please click here

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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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