Great Science of 2011: Three laureates cast their vote

With the end of 2011, another year of science has drawn to a close. For the last 12 months, the world of research has been churning away productively, making it almost impossible to say which discoveries will have the most significant impact, in the near future or down the road. Nevertheless, three laureates of the L’Oréal-UNESCO For Women in Science program have chosen the work from the past year that struck them the most, and tell us why.

Ana Belén Elgoyhen Institute for Research on Genetic Engineering and Molecular Biology, National Council for Scientific and Technical Research (CONICET), Buenos Aires, Argentina L’Oréal-UNESCO Award For Women in Science, 2008

Most appreciated in 2011: A method to treat tinnitus using targeted neural plasticity.

Tinnitus, a persistent phantom ringing or other noise in the ears, is a condition with very few treatment options.  A symptom, like a headache, that can have different causes, tinnitus has several underlying mechanisms, which remain poorly understood.  What we do know is that 10 percent of the population experiences tinnitus at some point in their life, and for one percent of people, the condition is truly debilitating.  It can be accompanied by other serious conditions—depression, sleeplessness, frustration, anxiety, irritation—that aggravate the situation terribly, explains Prof. Elgoyhen.  There are currently no pharmacological treatments approved for tinnitus, though the associated conditions may be eased with medications.  Counseling can help some patients learn to cope with tinnitus, but others simply go untreated.

2011, however, may have brought hope for tinnitus sufferers.  The team of Michael Kilgard, at the University of Texas at Dallas, has developed a potential therapy that relies on neural plasticity, the ability of the brain to reorganize connections between neurons.  This flexibility is, in fact, both part of the problem and part of the solution.

Noise-induced trauma is the main known cause of tinnitus.  Normally, the cells of the inner ear responsible for hearing, known as hair cells, detect sound waves from the environment and transmit this information to associated neurons in the auditory cortex of the brain.  Exposure to intense noise, though, can kill hair cells, and without the information they usually send to the brain, their target neurons die, as well.  The regions left empty in the auditory cortex are then invaded by neighboring neurons.  These are linked to surviving hair cells associated with a particular frequency, which now becomes overrepresented in the auditory cortex.  The result is a phantom sensation of sound at the frequency in question. The Texas team realized that the solution could be to undo the changes that had taken place in the brain, to restore the original tonotopy, or arrangement of frequencies along the auditory cortex.  They achieved this in rats by simultaneously stimulating an important cranial nerve and playing tones different from the tinnitus frequency.  Vagus nerve stimulation (VNS) is known to release chemicals in the nervous system, neurotransmitters, that are important for plasticity.  The method is already used to treat epilepsy and depression.  The experiment worked to eliminate the rats’ tinnitus (as demonstrated by their regained ability to detect a silence warning of a loud noise to come), by creating new connections in the brain to reestablish a normal representation of frequencies in the auditory cortex.

This method of stimulating plasticity to retune the auditory system is already being tested on patients by the team of Dirk De Ridder at the University Hospital Antwerp, Belgium.  Professor Elgoyhen feels that “if it works in humans, this will be a real breakthrough.  This is important for the potential applications in therapeutics for a pathology that has no real cure.”

Rashika El Ridi Faculty of Sciences, Cairo University, Egypt L’Oréal-UNESCO Award For Women in Science, 2010Most appreciated in 2011:  The characterization of the nuocyte, a newly discovered type of innate immune cell involved in allergies and parasitic infections.

First described in 2010 by a team at the MRC Laboratory of Molecular Biology (LMB) (Cambridge, UK), the nuocyte is a new name in the ranks of cells protecting our bodies from invasion.  Our immunity army uses chemical messengers, called cytokines, to communicate among its members.  Different cellular soldiers are activated by the messages, depending on the type of attack.  For instance, type 1 immunity is activated if the invader is present inside the organism’s cells (usually the case for intracellular bacteria or viruses); a type 2 reaction dominates the fight against a foreign presence outside of cells (as for parasites and toxins).  To launch this second type, the immune system’s T cells were known to produce some of the chemical messengers needed, but other sources had not been fully investigated.

Enter the nuocyte.  The team of Andrew McKenzie at the LMB, went looking for the main source of a particular type 2 immunity-activating cytokine, IL-13.  What they found was a cellular population that did not fit into any of the known lineages of immune cells (B cells, T cells, dendritic cells, etc.)  This new type of immune effector produces large amounts of IL-13, from where the nuocyte takes its name:  Nu is the 13^th letter of the Greet alphabet.

Research has continued on nuocytes, to examine and describe them further.  For instance, their crucial role in expelling helminths, parasitic worms, from the body has been revealed in mice.  In 2011, a link was also established between nuocytes and allergic asthma.  All allergies and hypersensitive reactions result from a predominantly type 2 immune response—the same that helps the body clear a parasitic infection.  In an allergic reaction, though, this response is overly or inappropriately active.  The McKenzie lab has recently shown that nuocytes are activated by allergens in an experimental model of asthma.  The cells then move into the lungs where they produce their namesake cytokine, IL-13, producing a hyper-reactive condition in the airways. Rashika El Ridi feels the identification and description of the nuocyte is the most important develoment of the last two years.  Their involvement in defense against parasites may play a role in her own work with schistosomiasis in Egypt, but she also feels these cells will be important for people in regions suffering less from this sort of infection.

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“Very importantly for people in Western countries…nuocytes might be critical for the induction of allergic reactions, especially in the gut, lungs and skin.”

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If this proves to be the case in humans, as early signs indicate, this new recruit to the immunity forces could represent an important target for future therapies.

Ameenah Gurib-Fakim Director of the Center for Phytotherapy Research (CEPHYR), Mauritius L’Oréal-UNESCO Award For Women in Science, 2007Most appreciated in 2011:  The sequencing, and open-access publication, of the genome of nearly 75 medicinal plants.

In the 1990s, Ameenah Gurib-Fakim recognized the importance of documenting the traditional knowledge of her native Mauritius and undertook a survey of all the island’s plant species being used by the locals.  Many plants, in the course of their metabolism, produce substances that have important applications in creating pharmaceuticals and in industry.  Dr. Gurib-Fakim notes that to take advantage of this rich natural laboratory we have a huge task ahead.  Many plants need to be tested, and quickly, before they, or the understanding of them, disappears.

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“The age bracket of locals with this knowledge, who know the uses and the right doses, is 50 to 70.  It’s a race against time.”

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For these reasons, Gurib-Fakim was delighted to see the first results of the PhytoMetaSyn Project published online this year.  A collaboration among 13 researchers from across Canada, the project has so far established the genetic profile of some 75 medicinal plants.  Because collecting useful substances directly from plants is greatly limited—by the small quantities produced, difficulties in harvesting, and the time needed for plants to grow—the goal is to harness the machinery of another organism to produce them for us. The PhytoMetaSyn team aims to identify the genes and enzymes responsible for the production of metabolites of medical or commercial interest.  When their synthesis is fully understood, the different elements in the process can be inserted into yeast cells, reconstructing the production channels of the plants, so that the yeast produces the same product in much larger quantities.

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“Usually, there would be a barrage of claims for intellectual property rights on this [sort of work]. I was very pleased to see they were making it public,” says Dr. Gurib-Fakim.

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“It’s a different mindset to put it in the public domain, and I’ve been very focused on this.  When I get this information from the lay people, I don’t keep it for myself—it’s too important.” She’d like to see this work continued for many, many more species.  “If we can reproduce this for other biodiversity hot spots, that will be mindblowing.”

Beyond the immediate commercial and medical applications of this genomic catalogue, Ameenah Gurib-Fakim cites the importance of the PhytoMetaSyn model for biodiversity.  A question currently being considered in Mauritius is whether to preserve the island’s biodiversity with a seed bank or a gene bank.  If the latter is chosen, the genetic profiling of plants will be very relevant.  Still, though, Ameenah underlines the continued importance of conservation.  “In 2011, new plant species were discovered in South America.  But if we go on destroying habitat, we will lose plants before we even know about them.”

It just goes to show that, in some ways, our work is never done.  And all the better for it:  There will always be new problems to solve, new discoveries to make, new ways to improve lives.  We’re looking forward to the coming year of science, and those that 2012 has in store.

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