Fruit flies like banana? Yes, but they might like alcohol more

Specific behaviors have been evolved to protect us from pathogens. An interesting study shows that flies drink for medication benefit.

        Sometimes when stimulated, our bodies give rise to mysterious unconscious response the occurance of which we don’t understand at all. For example, when watching horror movies we may show gooseflesh that push us to avoid those disgusting scenes. As a result, we feel relaxed and comfortable. These natural responses like gooseflesh are protective measures our bodies acquired during evolution. Similar behaviors include our unconscious fear of snakes, spiders, and other animals. These protective behaviors are reminiscent of our immune system that is evolved to use cells and molecules in our bodies to prevent invading parasites. For such a resemblance, behavioral immune system was coined to describe our behavioral response against outside hazards.

        In general, any biological behaviors protecting an organism from infection can be called behavioral immune. Medication, the use of substance or procedures by humans to fight infection, belongs to behavioral immune response.

        Behavioral immune system can explain some of our unconscious behaviors. For example, we sometimes dislike strangers for no reason. It is not for no reason. It is only a reason you don’t realize. Your behavioral system automatically discriminate different persons according to their faces, their poses, their age, their figure or their smell. Thus, behavioral immune may lead to prejudices against obese, elderly, short or disabled individuals. Moreover, behavioral immune system even contributes to xenophobia and ethnocentrism.   

        Flies are much smarter than we thought. They can use behavioral changes to adapt to environments. Flies often face the threat from wasps under natural environments. Alcohol is useful for flies to prevent infection from wasps. Although flies are not alcoholic, they do use alcohol to combat infection from wasps. A paper in this volume of Science¹ unveiled an interesting discovery about how flies tackle this threat from wasps by utilizing alcohol, showing us an example of self-medication of flies.

        Researchers placed 300 flies in cages containing two food dishes one of which was added with 6% alcohol by volume. In addition, flies were also housed with or without female wasps as a threat. Fly eggs were collected for counting from different dishes in each situation (with or without wasps). Interestingly, researchers found in the cages no wasps were provided, flies preferred laying eggs in dishes without alcohol. On the contrary, in dishes with wasps, flies laid more eggs in dishes with alcohol.

        This is not the whole astonishing story. Flies can even tell the gender of wasps. Female wasps are more dangerous. When flies were housed with male wasps, flies would just ignore them and did not show preference on alcohol containing dishes.

        Under the situation when wasps don’t exist, flies have some tendency toward alcohol. They prefer laying eggs in 3% alcohol. This means flies like a little bit alcohol. However, when realizing deadly wasps are nearby, they would like to try even 12—15% alcohol, the highest level of alcohol found in nature.

        How can flies tell wasps, especially more deadly female wasps are nearby? They may do this by olfactory or visual cues. To answer this question, flies harboring mutations that result in defects in olfactory or visual system were used to observe their alcohol preference. Researchers found flies with mutations in response to olfactory stimuli can still display alcohol preference whereas vision mutants of flies failed to show their fancy on alcohol. Thus, flies must use sight to sense the existence of wasps. A small protein called neuropeptide F has been shown to increase of alcohol tolerance of flies. In this study, researchers also found neuropeptide F played a role in transmitting visual signal from wasps to guide the alcohol preference behavior of flies.

        Flies can have a short time memory of the existence of wasps. When flies were first housed with female wasps and then wasps were removed, flies still displayed an alcohol preference at most 4 days after wasps were devoid.

        Flies’s behavioral immune system showed an vivid example how organisms have obtained ability to adapt to nature.

[1] Fruit Flies Medicate Offspring After Seeing Parasites. SCIENCE VOL 339 22 FEBRUARY 2013 947-950.

Note: the attached picture is from website: http://en.paperblog.com/mental-health-fruit-flies-turn-to-alcohol-when-sexually-frustrated-163917/

A big lotto for biologists

The biggest life sciences prize ever

        Nobel prizes have long been regarded as the most influential prizes in history not only because of its high selection standards but also because of its huge amount of reward which is about 1 million dollars allocated to at most 3 laureates. Nobel physiological prize will still take the lead in boosting life science in the near future. However, the number of the reward has been eclipsed by a new announced Breakthrough Prize which is worth 3 million dollars, the most lucrative annual prize in the history of science.

        The Breakthrough Prize was launched by Mark Zuckerburg, the founder of Facebook, Yuri Milner, the co-founder of Google, and Sergey Brin, a venture capitalist with an intention to combat cancer, diabetes, and other maladies. The establishment of this prize was ignited by the dramatic progression in some state-of-the-art technologies like genome sequencing. This year, the prize goes to 11 scientists from United States, Japan, Italy, and Netherlands. Among these recipients, some really famous names in life sciences are hit including Yamanaka, the 2012 Noble Laureate for his contribution in induced stem cell, and Robert A Weinberg, who discovered the first human oncogene Ras and first tumor suppressor Rb.

        It is still premature to evaluate any influence of this prize on life sciences. One point is clear, smart and energetic scientists will be encouraged to make great breakthrough for human health.

List of recipients of 2013 Breakthrough Prize.   

1 Cornelia I Bargmann
Torsten N Wiesel professor and head of the Lulu and Anthony Wang Laboratory of Neural Circuits and Behaviour at the Rockefeller University. Howard Hughes Medical Institute investigator.
For the genetics of neural circuits and behavior, and synaptic guidepost molecules.
2 David Botstein
Director and Anthony B Evnin professor of genomics. Lewis-Sigler Institute for Integrative Genomics at Princeton University.
For linkage mapping of Mendelian disease in humans using DNA polymorphisms.
3 Lewis C Cantley
Margaret and Herman Sokol professor and director of the cancer centre at Weill Cornell Medical College and New York-Presbyterian hospital.
For the discovery of PI 3-Kinase and its role in cancer metabolism.
4 Hans Clevers
Professor of molecular genetics at Hubrecht Institute.
For describing the role of Wnt signaling in tissue stem cells and cancer.
5 Titia de Lange
Leon Hess professor, head of the Laboratory of Cell Biology and Genetics, and director of the Anderson Centeer for Cancer Research at Rockefeller University.
For research on telomeres, illuminating how they protect chromosome ends and their role in genome instability in cancer.
6 Napoleone Ferrara
Distinguished professor of pathology and senior deputy director for basic sciences at Moores Cancer Centre at the University of California, San Diego.
For discoveries in the mechanisms of angiogenesis that led to therapies for cancer and eye diseases.
7 Eric S Lander
President and founding director of the Eli and Edythe L Broad Institute of Harvard and MIT. Professor of biology at MIT. Professor of systems biology at Harvard Medical School.
For the discovery of general principles for identifying human disease genes, and enabling their application to medicine through the creation and analysis of genetic, physical and sequence maps of the human genome
8 Charles L Sawyers
Chair, human oncology and pathogenesis programme at Memorial Sloan-Kettering Cancer Centre. Howard Hughes Medical Institute investigator.
For cancer genes and targeted therapy.
9 Bert Vogelstein
Director of the Ludwig Center and Clayton Professor of Oncology and Pathology at the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center. Howard Hughes Medical Institute Investigator.
For cancer genomics and tumor suppressor genes.
10 Robert A Weinberg
Daniel K Ludwig professor for cancer research at MIT and director of the MIT/Ludwig Centre for Molecular Oncology. Member, Whitehead Institute for Biomedical Research
For characterisation of human cancer genes.
11 Shinya Yamanaka
Director of the Centre for iPS Cell Research and Application, Kyoto University. Senior investigator and the LK Whittier Foundation investigator in stem cell biology at the Gladstone Institutes. Professor of anatomy at the University of California, San Francisco

Stay colder, live longer

        My mentor’s grandma passed away without any diseases at the age of 101. He told me his grandma is very nice and optimistic. She is also humorous. Her children kept calling her to say hello and she said each of her children wanted to be the first one to know she is dead by calling her. By the way, the grandma lived herself. The grandma likes drinking black coffee. Moreover, although my mentor is tall and strong, his grandma is pretty short. Optimism, humor, drinking coffee and being short have all been linked to longevity. But we cannot ignore another reason: my mentor is from Minnesota, a north state of United States where is very cold in winter. Cold temperature may have an important influence on longevity.

        Cold temperatures have been found to be related to extended lifespan of both poikilotherms and homeotherms. Like refrigerator storage of food can slower the decay, cold temperatures are believed to slowing aging in a similar way: reduce the rate of chemical reactions since life itself, in essential, is a kind of complicated chemical reactions. This hypothesis implicates that cold caused lifespan increase is a passive process. However, the truth is, life is not like food in the refrigerator and it makes active efforts to resistance cold temperature and to live longer.

         Researchers from University of Michigan tried to understand how cold temperatures are associated with lifespan by adopting C. elegans, a kind of worm which is a model animal frequently used for studying aging and senescence by scientists. They discovered that instead of slowing reactions, C. elegans struggle in cold temperatures to live longer. There exist some channels in cell surface of C. elegans which are sensitive to temperature drop. Once perceiving the change of temperature, these channels will activate some signaling pathways in cells and eventually a protein called DAF-16, which is a known lifespan extending factor, will be activated. Activated DAF-16 contributes to lifespan extension.

        Interestingly, cold-sensitive channels function mainly in intestine but not in other tissues. Neural system is evolved to respond environmental signals and is supposed to be a appropriate platform for cold temperature response. However, researchers in University of Michigan reported that it is intestine but not neural system in C. elegans to respond to temperature changes. In C. elegans, intestine is also the fat tissue. Thus, both intestine and fat tissues contribute to lifespan extension.

        What lesson can we learn from this cold associated lifespan extension? Considering the benefits of cold are only tested in C. elegans, it is premature to draw any similar conclusions in humans. At least in mice, lowering the whole body temperature of animals is known to extend lifespan. Anyway, people have performed ice bath for multiply purposes. Maybe we should add another one: you will live longer if you keep the habit of ice bath as along as you can.

[1] A Genetic Program Promotes C. elegans Longevity at Cold Temperatures via a Thermosensitive TRP Channel. Cell 152, 806–817, February 14, 2013.  

A new tool for genome editing

Bacteria defense system takes its place in human genome editing

        An RNA based nuclear acids degradation system found in bacteria and archaea was tamed for human genome editing.

        Genomes store information of life and human genome editing holds promise to improve human’ health and overcome diseases. Some available genome editing tools attract wide interests. Zinc finger nuclease (ZFN) technology and Transcription activator-like effector nucleases (TALENs), both of which were invented recently for genome editing, won the Method of the Year 2011, awarded by the journal Nature Methods. Lately, a new genome editing tool was released in Science¹.

        This new technology is based on an exogenous nuclear acid degradation system in bacteria and archaea. During evolution, bacteria and archaea face frequent and tremendous threats from environment. Exogenous nuclear acid constitute a main jeopardy because genomes of bacteria and archaea are not protected as well as that of advanced life. Bacteria and archaea thus develop a mechanism to combat exogenous nuclear acid. This system adopts RNA, which is characteristic of short repeats, and proteins to degrade invading nuclear acid. Shorted and repeated RNA is mainly responsible for the recognition of threatening exogenous nuclear acids whereas the RNA associated protein takes care of the degradation step. Although this nuclear acid degradation aims at invading DNA or RNA, they may be modified to target the human genome.

        Scientists in Havard Medical School engineer this nuclear acids degradation system in order to obtain targeted degradation of DNA sequence in human genome. The designed DNA sequence targeting interested DNA in human genome was linked to a DNA scaffold that facilitates the access of the protein responsible for degradation. The protein for degradation was also engineered to ensure location and high expression in human cells. The artificial DNA and protein are sent to human cells together. The designed DNA will recognize its corresponding DNA in the genome. Then the protein will function to cut the DNA in the genome. All mentioned above is what this bacteria originated system does. Other steps were finished by DNA repair system in human cells. Realizing a DNA damage (here it is broken DNA), the DNA repair system will try to repair it based on a similar DNA sequence, which is the special designed DNA in the artificial DNA donor in this case. The desired mutations, insertions, deletions will be thus possible.

        What are the advantages of this new genome editing tool compared to other tools? This system is easier and more efficient compared to ZFNs and TALENs. Both ZFNs and TALENs adopt specific proteins to recognize interested DNA sequence. It is tricky to design appropriate protein scaffold to match DNA in genome. The bacteria originated gene editing system uses DNA to recognize DNA in genome so it is easier to design DNA sequence. Actually, the authors have designed DNA sequences that able to cover about 40.5% exons in human genome. This bacteria originated DNA editing tool is also effective. In the Science paper, this new gene editing system achieved at most about 8% gene editing rate whereas TALENs resulted in not more than 1% gene editing rate.  

        A key standard to evaluate a gene editing tool is its specificity. That means it will favor interested genome regions but not other regions. Theoretically, this bacterial originated DNA editing system is specific because it usually uses 20 nucleotides, the length of which guarantees the required specificity in human genome, to recognize genome DNA. However, off-target effect of genome editing is still necessary. The Science paper did not resolve this concern.

        An exciting thing about this bacteria originated gene editing tool is there is more space to develop this technology. Both DNA scaffold and degradation proteins can be engineered to improve their efficacy and specificity.

Luck control

        People fail to realize how lucky they are except when some tragedies hit someone else. Every day, by watching TVs, surfing internets all of which report so many accidents, we got the idea that the world is full of risks. China is occupied by hazardous air; United States is discussing gun control; North Korean is testing nuke weapons; Solomon islands are experiencing earthquakes. Thus, fortune is not the arrival of good luck in the future, but the escape of bad luck in the past. Chinese cherish this kind of fortune by coining a word “houpa” that means the fear after the event. Western culture has also a similar expression: no news is good news.

        It makes more sense that we did not realize how lucky we are when it is about cancer. Everyone will develop cancer very early if their bodies fail to repair a great deal of DNA mutations caused by environments. Majority of people have no idea how many mechanisms in our body work together to protect us from cancer. For example, when DNA in a cell was hurt by UV, radiation or other stress, a protein called p53 will be activated to induce a cascade of events that lead to the death of the cell. So many similar proteins exist that DNA mutations will be eliminated under different circumstances. Every day, our bodies have fixed a great volume of mistakes in DNA without our realization.

        Among all hiding safeguard mechanisms preventing us from cancer, immune system is fundamental and vital. Immune reactions are tamed to help to reject cancer. Research of how to tame immune system for cancer treatment is called cancer immunotherapy. Historically, cancer is controlled by surgery, radiation therapy, chemotherapy, and latest targeted therapy. All these methods kill cancer cells using foreign materials without considering if these materials will also do harm to our body. Different from these methods, cancer immunotherapy focuses on provoking our immune system to work better to kill cancer cells. As a result, the side effects of cancer immunotherapy are less and the efficacy of it is better.

        Everyone has immune system so we are all lucky. But under some circumstances like cancer, luck is not enough. We need to control luck. Luckily, we are on the way.

Cancer: task impossible? Depending on what measurements we use

It is better to admit failing to win the war against cancer than fail to admit it.

        The Wall Street Journal published an article by Bill Gates a couple of days ago. The heading is so striking that I cannot help reading the contents. The title is “my plan to fix the world’s biggest problems”. However, after I went through the paper, I was a little bit disappointed because what Mr. Gates had declared as great plan for resolving biggest problems is actually very basic. Mr. Gates described the process of solving problems as simple 4 stages “setting clear goals, choosing an approach, measuring results, and then using those measurements to continually refine our approach” and emphasized that measurements are extremely important and the key to fix the biggest problems in today’s world: poverty, disease, lack of education and so on. Although it sounds simple, what Mr. Gates had said is indeed instructive. Setting goals is easy. People who tend to make New Year’s resolution will be able to know how easy to set goals. Selecting an appropriate approach is harder and requires smart thinking. But they are not in the same street with measuring and subsequent refining in term of the measuring. Measuring enables us to know how close we are from the goal.

        Where are we on the road map of cancer research in the light of current measurements we adopted?

       The answer, according to today's starndard, is probably we stay where we were decades ago in cancer research. About forty years ago, the president Richard Nixon set the goal to eradicate cancer by signing the National Cancer Act in 1971. The war on cancer campaign also fosters mounting cancer research. However, cancer incidence and death rates, which are two main standards to measure cancer research, keep unchanged during the past 40 years. The measurements have told us that cancer remains a big burden for Unites States. Moreover, some cancers show increasing incidence and death rates in United States and other countries. 
        It may be smart for us to accept the fact that we failed to win the war on cancer based on today's measurements. Only by accepting this fact, we can make some adjustment to better control cancer.

          Once we admit the fact that we failed the war on cancer, we will be able to figure out what we should do next. The direction for cancer control should be averted to cancer diagnostics and cancer prevention both of which entail broad and deep understanding of cancer genetic factors and environmental factors.      

        We might also need to adjust the standard we used to measure cancer control. Incidence rate and death rate of cancer have been used as golden standard for measuring cancer situation but may mask what we have achieved in cancer research. New measurements should be adopted in evaluating cancer control. Early detection rate, for example, may be used as a standard to measure cancer control and incorporated in cancer statistics.    

        Due to the aging population and deteriorating environment, the world will suffer tougher cancer burden. However, if we follow the direction of cancer diagnostic and prevention and adopt new measurements for cancer control, we might witness a tremendous progression in cancer control.

Discovery of Richard III's skeleton: DNA meets archaeology

Analysis of DNA in ancient remains enables us to reevaluate history.

        A 500-year-old remains found beneath parking lot in Greyfriars, Leicester was confirmed to belong to King Richard III, the last Plantagenet king of England, who is the subject of many works of literature including Shakespeare’s play Richard III.

        How was the skeleton regarded to be that of Richard III? On the one hand, ancient maps and records support that the parking lot which used to be a friary is actually the place where Richard III resided in. On the other hand, DNA test provided the decisive proof. DNA test was performed by comparing DNA from the remains discovered in Greyfriars and that from Canadian-born Michael Ibsen who is a direct descendent of Anne of York, Richard’s elder sister. Researchers responsible for this project have alleged: “It is the academic conclusion of the University of Leicester that beyond reasonable doubt, the individual exhumed at Greyfriars in September 2012 is indeed Richard III, the last Plantagenet king of England.”

        How can they be so sure that skeleton belongs to Richard III? Researchers did not disclose many details. But what they have announced is not convincing.

        The DNA test University of Leicester researchers have done must be like paternity testing which can tell if two individuals have a biological parent-child relationship by analyzing specific DNA information between two individuals that will be inherited from parent to child. In a standard DNA paternity test, usually a child, alleged father, and the mother are involved. The mother’s participation in the paternity test helps to exclude half of the child’s DNA, leaving the other half for comparison with the alleged father’s DNA. The DNA test about the identity of Richard III must be based on a method similar to paternity testing: comparing DNA information between the skeleton and Michael Ibsen. But at least two controls (controls with known information are used in biological experimental designs for ruling out or ruling in a candidate) should be set: first, an irrelevant random DNA should be incorporated as a negative control, and second, DNA sample from another descendent of Richard III should be incorporated as a positive control. These two controls are useful to rule out systematic errors.      

        DNA has played a role in identifying one of great names in history. In the future, DNA may be useful to disclose the health conditions of those great names in history that may shape the characters of those people or influence key events in history. In this way, the involvement of DNA in archaeology will change the landscape of archaeology.