Britain to make genome database


DNA molecule

Briton has taken the initiative when it comes to mass sequencing and are doing it in order to provide better health care opportunities to their residents.

Britain will be the first country to introduce a database of genetic sequences into a mainstream health service, officials say, giving doctors a more advanced understanding of a patient’s illness and what drugs and other treatments they need.

It could significantly reduce the number of premature deaths from cancer within a generation, Prime Minister David Cameron’s office said in a statement.

“By unlocking the power of DNA data, the NHS (National Health Service) will lead the global race for better tests, better drugs and above all better care,” Cameron said on Monday.

His government has set aside 100 million pounds ($160 million) for the project in the taxpayer-funded NHS over the next three to five years.

Harpal Kumar, chief executive of the charity Cancer Research UK, said the work would uncover new information from which doctors and scientists will learn about the biology of cancers and develop new ways to prevent, diagnose and treat them.

He said some targeted, or personalized, cancer treatments such as Novartis’ Gleevec, or imatinib – a drug for chronic myeloid leukemia – are already helping to treat patients more effectively.

Some critics of the project, known as the “UK genome plan”, have voiced concerns about how the data will be used and shared with third parties, including with commercial organizations such as drug companies.

Genewatch, a campaign group fighting for genetic science and technologies to be used in the public interest, has said anyone with access to the database could use the genetic codes to identify and track every individual on it and their relatives.

Cameron’s office said the genome sequencing would be entirely voluntary and patients would be able to opt out without affecting their NHS care. It said the data would be made anonymous before it is stored.

-Send in your suggestions at adeel@invitrovogue.com and share our news at your favorite social network.

Advertisements

Genetic Revolution and its impact on society: over view


Nobel Week pic

Today, a special webcast was broadcasted globally under the umbrella of Noble Week Dialogue. The webcast was titled Genetic Revolution and its impact on society and consisted of leading scientists and Nobel Laureates too. Noble Week Dialogue is a latest addition to the event pertaining to the run up to the Noble Prize main event.

The goal of the event was to bring together a select group of the world’s leading scientists, policy-makers and thinkers for a series of thought-provoking sessions and working groups on a topical science related theme. The theme for the 2012 Nobel Week Dialogue was The Genetic Revolution and its Impact on Society, a choice partly inspired by the fact that 2012 marks the 50thanniversary of the award of the 1962 Nobel Prize in Physiology or Medicine to Francis Crick, James Watson and Maurice Wilkins for their discovery of the molecular structure of DNA.

After introductory remarks, Eric Lander, esteemed scientists spoke on  Five Turns of the Double Helix, followed by an on stage interview with James Watson by Matt Ridley. Then Helga Nowotny spoke on  A Social Scientist in the Land of Genomic Promise followed by Steven Chu on The Role of Genomics in Energy and the Environment. This followed panel discussion by imminent scientists. The entire conference and the content has been summarized below:

1. Eric Lander: How Biology Entered The Information Age

Eric Lander was one of the leaders of the effort to sequence the human genome, and has continued to work on various follow on projects through his involvement with the Broad Institute, a leading sequencing center. So, he makes an excellent choice to provide some perspective about how the growing availability of genomes has driven the biological sciences over the last decade.

“How do you ask how to read DNA?” Lander asked. “You ask the master—the cell. The cell is in the business of reading the information in DNA.” Molecular biology and biotechnology developed around the purification and use of the proteins used by the cells themselves to manipulate DNA.

Conceptually, Lander said, the key step was the development of a hierarchal map. Lay out genetic markers on a map, identify the DNA associated with those markers, and then dig down into the actual DNA sequences. The first human genetic map appeared in 1987, and that set the stage for the genome sequencing to kick off in earnest in the 1990s. The final draft was announced in 2003, on the 50th anniversary of the Watson and Crick paper.

More detail can be read at: http://www.nobelweekdialogue.org/science/eric-lander-how-biology-entered-the-information-age/

2. Nowotny-Horizon 1620 and beyond

Nowotny compared the new EU funding strategy, Horizon 2020, to what she called “Horizon 1620″. This was the year which Francis Bacon “sailed through the pillars on knowledge”. Bacon and others promised “the effecting of all things possible”. She cited an important part of this enlightenment era as the belief in progress.

Looking back at the industrial revolution, Nowotny said “it was only when [technology] came together with science that it became the driver that we see today”.

Towards the end of the talk, Nowotny spoke about ethics and promises. Politicians across the world should listen to this wise nugget: “Be careful with promises we make and not to betray them.”

3. Understanding gene environment interaction

In the panel discussions that took place after the main lectures were interesting and added more flavor to the debate.

he moderator, Göran Hansson, posed the question: How far are we from understanding these interactions?

Eric Lander raised a really interesting point that the general public perceive genetics as risk factors of disease. He disagreed with this impression saying “genetics is here to understand mechanism”. It seems that geneticists need to portray as Lander said that “genes and environment works inextricably together”.

Using lung cancer as an example, Lander said that we can understand the genes involved but we need to address the huge environmental factor: smoking. He added that we need to communicate science better to get people to stop smoking and understand this obvious environmental effect.

In some diseases, I thought it was brilliant that this panel of geneticists were willing to question the focus on genetic research. Joe Goldstein said “we have to deal with patients with diseases that have strong familial components”. He cited colon cancer as an example where a colonoscopy is much better than getting your genome sequenced.

If you look at cancers in a population, the hereditary impact varies between 3 and 10%. Using breast cancer as an example, Mary Claire King said that by working with families that are severely affected by the disease, they were able to isolate the genes involved: BRCA1 and the many others found since. She said Europe was better at testing for these mutations but the United States needed to improve. If these mutations are tested in women, these cancers can be prevented. I think this is true for many new technologies involving genetics – governments are slow to adopt them which to me seems short-sighted given the costs involved downstream for treatment.

This short-term focus was also raised by Bert Vogelstein who said that “we, as a society, are so focused on curing these advanced cancers that we don’t see other ways to tame the beast”.

This was such an fascinating discussion. Now that we know so much more about the genetic mechanisms, it seems that looking towards the impact of the environment is more possible. Göran Hansson  summed this up saying “we are probably in for a new era of diagnostics”.

4. Future of Human Biology

There was a strong focus on the continued need for fundamental science during this afternoon’s session, Human Biology: The Great Deal We Don’t Know and How to Discover It.

The worry about reduced funding for fundamental research was evident during each speakers input to the conversation on the future of research on human biology. Taking this a step further, Christiane Nüsslein-Volhard said that “we need to know more about general biology”.

The moderator, Bruce Alberts, said that much of the funding for biochemical research is by people who have had these diseases e.g. cancer survivors. This has an adverse impact according to the Editor-in-Chief of Science. He often hears people say: “Why should the public tax money pay for scientists satisfying their curiosity?”

Craig Mello added that those very naive curiosities often result in huge discoveries. He mentioned being in awe of the fact that the genetic code is similar across organisms and finding out that the insulin gene can be read by bacteria. I interviewed him earlier this week and he spoke about this: read here.

“Curiosity is a basic must for scientists” said Nüsslein-Volhard. She recommended that if you’re not curious, don’t do science. Here’s a great formula she gave for good research:

Curisosity + Good Problem + Bit of Smartness = Good Basis for Research

Mello said that the reduction can be blamed on the limited resources we now have. Given the choice between funding research that might get into clinics next year or a long-term project that could revolutionize medicine, review panels are choosing the applied clinic-focused research. He said that funding in the United States is flat despite the increased need to understand the new knowledge available. “This is really unacceptable and it really threatens our ability to do the basic science for the next 10 years”.

Asked how we can change this, Steven Chu said that leaders have to be convinced that you have to make investments into the future. This is happening in the United States according to Chu who used the saying “you don’t eat your seed corn”. Mello added that we need to do a better job at communicating with policy makers and scientists must keep track of the impact of their research.

This is yet another conference where this debate is a hot topic. Every Nobel Laureate and prominent scientist that I have heard speak about this thinks there is a problem with fundamental science funding. However, policy makers in many countries think we need more applied science. Perhaps this is a take home message for policy makers!

5. Genetics and Agriculture

The afternoon stream was a panel session moderated by Matt Ridley, with panellistsDominic BartonTorbjörn Fagerström, Louise FrescoChristiane Nüsslein-Volhard andTikki Pang (Pangestu).

We began with two audience polls, a show of hands proposed by Ridley: how many people are in favour of GM foods? An overall majority in favour. Louise Fresco suggested a poll on how many are optimistic we can feed the world in 2050, again a majority. These two questions highlight the main themes of the discussion, that of the base issue of GM acceptance, and the need for which GM will be required to feed a growing population.

Fresco opened by stating the GM debate by highlighting that most of the GM work has gone into herbicide resistance, which ironically has generated the most resistance in another area – society. In recent years Bacillus thuringiensis toxin (Bt) has had a positive effect on health and ebnvironment, it has allowed small farmers in India and China to reduce use of pesticides, with a positive effect on health and environment. Can we extend that same duel benefit to other crops?

However Fagerström raised the more fundamental issue, the question of why is there this resistance in society? Especially given the empirical support for GM not being a problem is very strong. How did we end up here? Nüsslein-Volhard believes the issue is rooted in a resistance against science, rather than GM itself. Why do people not trust scientists? Why are politicians inclined to embrace the more fluffy ‘green’ organisations rather than scientific manifestos? The problem is that there is deeply rooted mis-trust brought about by a lack of education. I could liken it to the issues raised by Helga Nowotny this morning on the fulfilment of promise – genomic technologies meeting a pre-genomic society. After all, we have the genomes for several crops now (e.g. rice) so we actually know what we are changing.

The other issue is that in modern, western farms, farmers are paid whether their crop fails or succeeds; they just don’t need to care about more efficient production. In fact, if they increase production – the surplus just floods (and destablises) the developing countries. However, local action on governments in countries where these technologies are being developed negatively effects the prospects for these products in these developing countries.

Fresco highlighted that in discussing GM people don’t go into the details; there is too much generalisation. Focus on specifics, like perhaps the potato. We’re not talking about wide-crosses here (i.e. jellyfish genes in vegetables), but in fact practise sys-genesis, the back crossing with ancestral Andean types of potato that are resistant to phytophthora blight. We should show that GM can be close to the original, rather than some mutant chimera. Torbjörn agrees, and suggests that GM should be judged crop by crop like anything else. It’s like saying you are against electricity, just because some electrical items can be bad!

Another problem is that societies that most object to GM do not readily feel the tangible benefits of GM. Is the a comparable objection to GM cotton that we wear, or the idea of fast growing GM trees, or transgenic mosquitoes that don’t vector diseases such as Dengue. When we feel the advantage, so our perceptions of ‘risk’ diminish?

All in all, it was a productive event and provided a balanced point of view from scientific perspective and generally too.

Send in your suggestions at adeel@invitrovogue.com and share our news at your favorite social network.

 

Kenya Bans GM Food Trade


GM-Food-300x300Research institutions, Universities and consumers are biggest losers in a new directive by the Government to ban trade and importation of genetically modified foods (GMOs), experts say.

Moi, Kenyatta, Jomo Kenyatta University of Agriculture and Technology (JKUAT) and Nairobi universities have been laying foundation for biotechnology studies. For instance, Kenyatta University had review existing biochemistry and biotechnology programs to take advantage of recent legislation passed by the Government in support of GMOs.

The reviewed programmes at Kenyatta take effect in the first semester of 2012/2013 academic year. In an announcement that might slow such development, Public Health minister Beth Mugo last month ordered for the ban of GMO foods in Kenya.

Citing safety issues, she called on all government regulators and agencies involved in overseeing the importation of food products to with immediate effect comply with the directive and beef up security at the port and along border points to prevent any entry of the GMOs into the local market.

Dr Silas Obukosia, Director Regulatory Affairs at Africa Harvest said the move was misinformed and likely to deny Kenya the opportunity to increase food production through modern technology.

Friendly laws

He said efforts by universities to enhance their biotechnology programs and building capacity in the area might go into waste if the decision by the minister is not annulled.

“Mugo’s ban on the importation and trade of GMOs due lack of evidence regarding their safety is puzzling,” he said. “This is because major investments such as the approval of the National Biotechnology Development Policy by the Cabinet in 2006, and the enactment of the Biosafety Act in 2009, and gazettment of three different biosafety regulations in 2011 have been made to address the issue of safety,” he said. “A lot of money has been pumped in by universities in creating masters and PhD programmes in biotechnology which need to be supported by friendly laws.”

A degree course in biotechnology and biosafety was launched in Moi University in 2009. JKUAT has developed a Master of Science in Biotechnology. Kenyatta runs both undergraduate and postgraduate courses in biotechnology. Kenya is among the few countries in Africa leading in the fusion of technology in food production, this is with an aim of creating disease and drought resistant varieties.

Currently crops such as maize, cotton, cassava, sweet potato, and sorghum are in confined field trials.  Kenya plans to join the league of African countries that have commercialised Bt cotton in 2012.  Kenya Agricultural Research Institute (KARI) scientists had completed field trials of Bt cotton at Mwea in the Eastern Province of Kenya.

Send in your suggestions at adeel@invitrovogue.com and share our news at your favorite social network.

 

New Class of Antibiotics for MRSA


MRSA pic

The Mechelen, Belgium biotech company,Galapagos, says they discovered an entirely new class of antibiotics that may offer treatment against multiple drug-resistant infections, including 100% of all drug resistant Staphylococcus aureus, including MRSA,according to a company news release Nov. 26.

According to the release, the propriety antibiotic works by inhibiting the target DNA pol IIIα, an enzyme present in all bacteria and essential for their growth; this target is absent in humans. The novel mode of action – inhibition of DNA pol IIIα – may be used to explore a variety of novel antibiotics, targeting bacteria for which resistance to current antibiotics has emerged.

Using this novel target, Galapagos has selected a first candidate antibiotic, CAM-1, to enter drug development. CAM-1 was tested against more than 250 different bacterial strains and effectively killed 100% of all drug resistant S. aureus, including MRSA. CAM-1 shows better efficacy than standard antibiotics, as shown by in vivo bacterial infection models. Galapagos aims to enter the clinic in the first quarter 2014, with a Proof of Concept study thereafter.

Chief Scientific Officer of Galapagos, Dr. Piet Wigerinck said, “Our antibiotics have a novel mode of action which brings all tested MRSA strains to a complete halt. Combined with a diagnostic test, these compounds could bring a real solution to MRSA infections.”

According to the Centers for Disease Control and Prevention, Methicillin-resistant Staphylococcus aureus (MRSA) is a type of staph bacteria that is resistant to certain antibiotics called beta-lactams. These antibiotics include methicillin and other more common antibiotics such as oxacillin, penicillin, and amoxicillin. In the community, most MRSA infections are skin infections. More severe or potentially life-threatening MRSA infections occur most frequently among patients in healthcare settings.

Treatment of MRSA may include incision, drainage (depending on the type of infection) and antibiotic therapy.

Send your suggestions at adeel@invitrovogue.com and share our news at your favorite social network.

 

 

Pulsating Mechanism as a Stress Response


Genomes are not merely consisting of A,T, G and C. There is so lot more to them than we know. A comparatively simpler genome of a bacteria like Bacillus subtilis can respond to a wide array of changes in its environment. Our knowledge of the exact mechanism is not complete as yet since there is a need for a better system of studying gene-protein interaction. Take, for instance the stress response that bacteria take in cold. While we resort to heaters for tackling the cold, the bacteria does the same! This is what has been reported recently by researchers at Caltech.

Fig: Florescent proteins are used to study the pulsating mechanism.

Previously we assumed that in response to stress, bacteria generally go to a dormant state-meaning that they shift from one state to another. However, new studies shows an active utilization of the existing system to tackle the stress.

What the researchers say?

Researchers at the California Institute of Technology (Caltech) are finding that cells can respond using a new kind of pulsating mechanism, instead of just shifting from one steady state to another and staying there. The principles behind this process are surprisingly simple, the researchers say, and could drive other cellular processes, revealing more about how the cells—and ultimately life—work.

The Experiment

In their experiment, the researchers studied how a bacterial species called B. subtilis responds to a stressful environment—for example, one without food. In such conditions, the single-celled organism activates a large set of genes that help it deal with hardship, by aiding cell repair for instance. Previously, biologists had thought the bacteria would handle stress by turning on the relevant genes and simply leaving them on until the stress goes away.

Instead, the researchers found that B. subtilis continuously flips these genes on and off. When faced with more stress, it increases the frequency of these pulses. The pulsating action is like switching your heater on full blast for a brief period every few minutes, and turning it on and off more frequently if you want the house to be warmer.

The Underlying Mechanism: Genetic Circuit

To make their finding, the researchers introduced a chemical to B. subtilis that inhibits the production of ATP, the energy-carrying molecules of cells. The team found that the stress induced by this chemical triggers interactions within a set of genes—collectively called a genetic circuit. This circuit, which contains a set of positive and negative feedback loops, generates sustained pulses of activity in a key regulatory protein called σB  (“sigma B”). The researchers attached fluorescent proteins to the circuit, causing the cells to glow green when σB was activated. By making movies of the flashing cells, the team could then study the dynamics of the circuit.

The key to this pulsating mechanism is the variability inherent in how proteins are made, the researchers say. The number of copies of any specific protein in a given cell fluctuates over time. The bacterial gene circuit amplifies these molecular fluctuations, also called noise, to generate discrete pulses of σB activation. The stress also activates another key protein that modulates the pulse frequencies.

More on the Genetic Circuit

By turning a steady input (the stress) into an oscillating output (the activation of σB) the genetic circuit is analogous to an electrical inverter, a device that converts direct current (DC) into alternating current (AC), explains Michael Elowitz, professor of biology and bioengineering at Caltech, Howard Hughes Medical Institute investigator, and coauthor of the paper. “You might think you need some kind of elaborate circuitry to implement that, but the cell can do it with just a few proteins, and by taking advantage of noise.”

This work provides a blueprint for how relatively simple genetic circuits can generate complex and dynamic behaviors in individual cells, the researchers say. “We’re excited to think that similar mechanisms may occur in other cellular processes,” Locke says. “It’d be interesting in the future to see which aspects of this circuit architecture also appear in more complex systems, such as mammalian cells.”

The paper has been titled “Stochastic pulse regulation in bacterial stress response” and was published in Science in October. (http://www.ncbi.nlm.nih.gov/pubmed/21979936)

-Caltech Media Relations

Send in your suggestions at adeel@invitrovogue.com and share our news at your favorite social network.

Micropyramids to capture living cells


While pyramids are generally considered to be a grandeur construction, they are being used on micro level to capture live cells. The underlying principle is that since these micro pyramids have open walls, it is easier to living cells to interact-and easier for us to study them. This has been made possible through 3D Nano Fabrication.

Scientists of the research institutes MESA+ and MIRA of the University of Twente in The Netherlands present this new technology and first applications in the journal Small.

Most cell studies take place in 2-D: this is not a natural situation, because cells organize themselves in differently in the human body. If you give the cells room to move in three dimensions, the set-up is closer to what we find in nature. This is possible in the ‘open pyramids’ fabricated in the NanoLab of the MESA+ Institute for Nanotechnology of the University of Twente.

How is the pyramid being used?

If you join a number of flat silicon surfaces to form a sharp corner, it is possible to deposit another material on them. After having removed the the bulk of the material, however, a small amount of material remains in the corner. This tiny tip can be used for an Atomic Force Microscope, or, in this case, for forming a micro pyramid.

How are the cells captured?

In cooperation with UT’s MIRA Institute for Biomedical Technology and Technical Medicine, the nanoscientists have explored the possibilities of applying the pyramids as ‘cages’ for cells. First experiments with polystyrene balls worked out well. The next experiments involved capturing chondrocytes, cells forming cartilage. Moved by capillary fluid flow, these cells automatically ‘fall’ into the pyramid through a hole at the bottom. Soon after they settle in their 3-D cage, cells begin to interact with cells in adjacent pyramids. Changes in the phenotype of the cell can now be studied in a better way than in the usual 2-D situation. It is therefore a promising tool to be used in tissue regeneration research.

Possible Extension of the Idea

The Dutch scientists expect to develop extensions to this technology: the edges of the pyramid can be made hollow and function as fluid channels. Between the pyramids, it is also possible to create nanofluidic channels, which could be used to feed the cells.

Article: Erwin J. W. Berenschot, Narges Burouni, Bart Schurink, Joost W. van Honschoten, Remco G. P. Sanders, Roman Truckenmuller, Henri V. Jansen, Miko C. Elwenspoek, Aart A. van Apeldoorn, Niels R. Tas. 3D Nanofabrication of Fluidic Components by Corner LithographySmall, 2012

-Adeel

Send in your suggestions at adeel@invitrovogue.com and share our news at your favorite social network.

The importance of invariant natural killer cells


Malaghan Institute of Medical Research has made a translational breakthrough. A study done there has revealed that boosting the activity of a rare type of immune cell could be a better method to vaccinate patients who have chronic lymphocytic leukaemia (CLL).

About CLL:

CLL is the most common blood cancer across the world and in New Zealand too. The prevalence of CLL increases with age, reaching 1 in 400 in individuals over 70 years old. Although many people with CLL never need treatment, a significant number of patients are diagnosed at a young age or have aggressive disease, exhausting conventional therapies.

Available Treatments:
Haematologist Dr Robert Weinkove says that bone marrow transplantation is the only curative treatment for CLL and involves replacing the immune system of patients with that of a matched donor.

“Part of the reason that bone marrow transplants work is that the new (donor) immune system recognises the leukaemia cells as foreign and destroys them,” says Dr Weinkove. “This is a good demonstration of how immune therapies can successfully cure established cancers in humans.”

Disadvantage with transplants:
Bone marrow transplants are not without their problems however. Not all patients find a donor; patients are prone to infections for months or even years afterwards; and the treatment itself can be so toxic that it is not suitable for many patients.

Invariant Natural Killer T Cells:
“To identify more targeted, low risk immune therapies, we focused on a rare type of immune cell called invariant natural killer T (iNKT) cells,” says Dr Weinkove.

Previous research at the Malaghan Institute and overseas has shown that iNKT cells can be activated by a compound called α-galactosylceramide (α-GalCer), which was first found in a Japanese marine sponge. This leads to significantly enhanced tumour-specific immune responses.

While iNKT cells are promising targets for immunotherapies, in many cancer patients iNKT cell numbers are either reduced, or the cells do not work properly. Since iNKT cells had never been characterized in patients with CLL before, Dr Weinkove launched a collaborative study between the Wellington Hospital Blood and Cancer Centre and the Malaghan Institute, to determine the number, phenotype and function of iNKT cells in people with this form of leukaemia.

Study:
Between 2008 and 2011, Dr Weinkove collected blood samples from 40 patients with CLL and from 30 healthy volunteers of a similar age, from the greater Wellington region. He then undertook a series of laboratory tests to compare the number and function of the iNKT cells from these individuals.

This study, which has recently been published in the open-access, international scientific journal Haematologica, constitutes the first comprehensive investigation of iNKT cell numbers and function in patients with CLL.

“We found that we could detect and isolate iNKT cells from individuals with CLL, and that these cells were able to respond to α-GalCer,” says Dr Weinkove. “This is important because it suggests that iNKT cells remain functional in these patients, and that targeting them with treatments like α-GalCer might be a way of enhancing their ability to drive anti-cancer immune responses.”

The Next Step:

Having shown such great promise in the laboratory, the next step will be to see if these results can be replicated in patients.

“Designing and running safe clinical trials is a major undertaking, but we are exploring a number of ideas, including the possibility of giving α-GalCer to patients with blood cancers to boost their immune responses,” says Dr Weinkove.

This work complements the dendritic cell cancer vaccination programme at the Malaghan Institute.

This research was supported by grants from the Leukaemia & Blood Foundation, Genesis Oncology Trust and NZ Lottery Grants Board. Dr Weinkove also received support from a Genzyme New Investigators Scholarship through the Haematology Society of Australia and New Zealand.

Download Paper:

The paper can be downloaded from here: InVariant Natural Killer Cells

-Adeel

Send in your suggestions at adeel@invitrovogue.com and share our news with your favorite social network.