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Permalink 12:26:33 am, by Tom, 412 words, 1960 views   English (UK)
Categories: Information

Looking back, looking forward

As 2008 comes to a close it's a good opportunity to look back on the year, and what a year it's been. Support for animal research at Oxford remains high and in November the University announced that work on the construction of the new biomedical facility has been completed. This new facility, which prompted angry and sometimes violent opposition from animal rights campaigners but also unprecedented demonstrations of public support from scientists, students and ordinary members of the public, will enable Oxford scientists to build on an excellent record that sees work of many of its medical researchers rated as either world-leading or internationally excellent.

We're also excited to see that the prestigious research journal Science has named reprogramming cells as its "Breakthrough of the year" (1), and notes that:

"The feat rests on a genetic trick, first developed in mice and described 2 years ago, in which scientists wipe out a cell's developmental "memory," causing it to return to its pristine embryonic state and then regrow into something else. In 2008, researchers achieved another milestone in cell reprogramming. In an elegant study in live mice, they prompted cells to make the leap directly from one mature cell into another--flouting the usual rule that development of cells is a one-way street. These and other advances in tweaking cells to assume new identities add up to make the now flourishing field of cellular reprogramming Science's Breakthrough of the Year."

We are delighted to see that this exciting work, which we have discussed on a couple of occasions of occasions on our science blog and more recently on the blog of our sister organization Speaking of Research, recognized in this way. Another interesting technique we reported on, the use of advanced GFP technology to track embryonic development was one of 10 runners up, ranging from the detection of planets outside our solar system to calculating the forces that bind sub atomic particles, chosen by Science. We all know that animal research is held in high regard by the scientific community, but the decision made by Science is further proof if any were needed that it is held in the highest regard.

With new members and continuing support from students at Oxford and beyond we will strive to build on our successes and make 2009 another year to remember. We wish all our supporters a very Merry Christmas and a peaceful and prosperous New Year!


Paul Browne

1) Vogel G. "Breathrough of the year: reprogramming cells" Science Volume 322 (5909), pages 1766 1767 (2008) DOI: 10.1126/science.322.5909.1766


Permalink 01:18:17 pm, by Tom, 900 words, 1887 views   English (UK)
Categories: Information

Fighting the scourges of humanity

The past week has seen some interesting news on efforts to combat three diseases that blight the lives of millions in the world today.

The most exciting news was that in two studies (1,2) published this week in the New England Journal of Medicine the malaria vaccine RTS,S passed a major milestone in its development by showing that it could safely protect infants against malaria infection. These results pave the way for larger phase III studies, and if these are successful RTS/S could soon be an important component of ongoing anti-malaria strategies alongside insecticide-treated bed nets and recently developed artemisinin-based combination drugs.

The clinical development of RTS,S has been a long process that began as a collaboration between the Walter Reed Army Institute of Research (WRAIR)and GlaxoSmithKlein in the late 1980's. Two key discoveries guiding the development of RTS,S were the finding in mice (3) that in order to immunize against malaria infection it is necessary to stimulate a cell-mediated immune response in addition to an antibody-mediated response, and the simultaneous discovery by scientists at WRAIR that incorporating a hepatitis B surface antigen into the malaria vaccine construct improved its ability to induce an immune response in mice and rabbits (4).

While the news of RTS,s good performance in clinical trials is to be welcomed it is worth noting that it does not protect everyone, with the best protection rates being in the 60% range, so ideally it should be combined with other vaccines that target different stages of the malaria parasite's life cycle. Research into such vaccines being performed at several institutes worldwide, including the Jenner Institute in Oxford whose work I discussed earlier this year.

Another medical research story that has been widely reported is a study indicating possible role for the cold sore virus HSV1 in Alzheimer's disease. The interesting thing here is that while there has been a lot of research done on the role of aggregation of beta-amyloid into extra cellular plaques and tau proteins into intracellular tangles, there have been few clues as to what causes these proteins to aggregate in the first place. This work suggests that HSV1 infection may trigger the formation of beta-amyloid plaques. The research published this week involved analyzing the brains of Alzheimer's patients and non-alzheimer's controls, but as the authors point out in the paper the presence of HSV1 in amyloid plaques is not in itself proof of a role for HSV1 in the plaque formation, so they refer readers to an earlier paper (5) where they demonstrated that mice infected with HSV1 developed beta-amyloid plaques in their brains, and in vitro studies that show that HSV1 can increase the activity of enzymes responsible for producing beta-amyloid. The observation that there is a causal relationship between HSV1 infection and the development of beta-amyloid plaques spurred Professor Itzhaki and her colleagues to examine human brains for signs of an association between HSV1 infection and Alzheimer's disease. This work is at an early stage, and while HSV1 infection may be a trigger it is likely that other factors such as an individuals genetic makeup are also important in the development of Alzheimer's. If the involvement of HSV1 is supported by further studies anti-viral drugs may be used to help slow the progression of the disease, and perhaps even stop it entirely if administered early enough.

Finally scientists at the Yerkes National Primate Research Center in Atlanta have shown that a novel way of fighting viral infection can stave off death from AIDS in SIV infected monkeys (6). This line of research was kicked off a decade ago by work undertaken in mice infected with the rodent-borne lymphocytic choriomeningitis virus showing that exhaustion of a population of immune cells termed CD8+ T-cells which target viruses led to loss of the ability to control infection. An increase in the amount of a receptor protein called PD-1 on CD8+ T-cells was associated with exhaustion and that their anti-viral activity was restored by treating the mice with antibodies that blocked PD-1. Subsequently researchers found that in SIV infected monkeys and HIV patients increased PD-1 is also associated with CD8+ T-cell exhaustion and progression to AIDS, but until now it has not been clear if blocking PD-1 will help prevent progression of AIDS. So far the results from Yerkes are encouraging, and further testing is now underway to determine whether anti-PD-1 treatment remains effective over longer periods of time, and whether it can also be used to treat other chronic viral infections such as hepatitis C.

All in all an interesting week!


Paul Browne

1) Bejon P. et al. "Efficacy of RTS,S/AS01E Vaccine against Malaria in Children 5 to 17 Months of Age" NEJM Vol.359, pages 2521-2532 (2008) DOI:10.1056/NEJMoa0807381

2) Abdulla S. et al. "Safety and Immunogenicity of RTS,S/AS02D Malaria Vaccine in Infants" NEJM Vol. 359, pages 2533-2544 (2008) DOI:10.1056/NEJMoa0807773
3) Schofield L. "Gamma interferon, CD8+ T cells and antibodies required for immunity to malaria sporozoites" Nature Vol. 330(6149), pages 664-666 (1987) DOI:10.1038/330664a0

4) Rutgers T. et al. "Hepatitis B Surface Antigen as Carrier Matrix for the Repetitive Epitope of the Circumsporozoite Protein of Plasmodium Falciparum" Biotechnology Volume 6, pages 1065 - 1070 (1988) DOI10.1038/nbt0988-1065

5) Wozniak M.A. et al. "Herpes simplex virus infection causes cellular beta-amyloid accumulation and secretase upregulation" Neurosci Lett. Vol. 429(2-3), pages 95-100 (2007) DOI:10.1016/j.neulet.2007.09.077

6) Velu V. et al. "Enhancing SIV-specific immunity in vivo by PD-1 blockade" Nature, Published online 10 December 2008 DOI:10.1038/nature07662


Permalink 12:15:53 pm, by Tom, 512 words, 1863 views   English (UK)
Categories: Information

From organ development to tissue engineering

Over the past year we have reported on how scientists are discovering how to engineer tissues and cells to treat disease, and how animal research plays a key role this new field of medicine.

It seems appropriate that Science, one of the world's top scientific journals, has this week published a special edition that surveys recent progress in our understanding of how our organs develop. This basic research underpins the use of stem cells in medicine and tissue engineering, and the reviews that make up the special report provide an excellent insight into how much we have learned in the past decade, and how much we have yet to learn. Amid the discussion of different theories about how particular cells and tissues develop and the strength of the evidence supporting those theories one thing becomes abundantly clear; the importance of research on animals as diverse as the fly, zebrafish, chick and mouse. For example while discussing one area of research, the process of branching morphogenesis where cells expand their surface area by forming extensions during organ development, Pengfei Lu and Zena Werb (1) observe that:

"Due to their structural simplicity and genetic accessibility, the Drosophila tracheal and air sac systems have given insight into understanding how epithelial branching occurs in the more complex organ systems of vertebrates. With recent technical advances, including modern mouse genetics, cell fate–mapping, mosaic analysis, and live imaging of organ cultures, our understanding of vertebrate branching mechanisms has dramatically improved."

An excellent example of ongoing research into organ development is provided by scientists at UCLA (2) who have shown in developing mouse embryos that the hematopoietic stem cells that produce the cells of the blood originate in the endothelial cells that line the inside of blood vessels. This discovery will help scientists who are trying to find ways to produce hematipoietic stem cells from the cells of a patient's own blood vessels in the lab for use in transplants, for example after treatment for leukemia. If that is successful it may well benefit from another piece of work published this week (3), this time by scientists at Harvard University. The Harvard team used sophisticated imaging techniques, including the use of GFP labeled cells, to map the fate of hematopoietic stem cells and their derivatives that were injected into mice. This work, which demonstrates what happens to the cells under different conditions in unprecedented detail, should enable scientists to develop new techniques to optimize hematopoietic stem cell transplant.

Regenerative medicine and tissue engineering are exciting areas of research, and will no doubt grab many headlines in coming years; its worth remembering all the animal researchers who work hard behind the scenes to make the breakthroughs happen.


Paul Browne

1) Lu. P and Werb Z. "Patterning mechanisms of branched organs" Science Vol. 322 (5907) pages 1506-1509 (2008)
DOI: 10.1126/science.1162783

2) Zovein A.C. et al. "Fate tracing reveals the endothelial origin of hematopoietic stem cells" Cell Stem Cell, Vol. 3 (6), pages 625-636 (2008) DOI:10.1016/j.stem.2008.09.018

3) Celso C.L. et al. "Live-animal tracking of individual haematopoietic stem/progenitor cells in their niche" Nature, Published online 3 December 2008, DOI:10.1038/nature07434

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