Scientists Discover What Makes The Same Type Of Cells Different

A research team led by Lucas Pelkmans at ETH Zürich has managed to decipher a well-known phenomenon that had, until now, remained unexplained: why cells of the same type can react differently, and what the reason for this is.

The properties of a cell population determine the different cell activities observed in cells of the same type. This is the conclusion drawn by a research team lead by Lucas Pelkmans, professor at the Institute for Molecular Systems Biology at ETH Zürich. The scientists examined the cause of the well-known phenomenon of cell heterogeneity. Until now, the reasons behind the different reactions seen in cells of the same type had not been scrutinised.

No random distribution

After three years of intensive development and research work, researchers have developed a computer-supported process, which allows them to observe the processes behind the variability of individual cells in cell cultures with millions of cells for the first time, and uncover the secret behind these processes. Until now, cell variability was simply called “noise”, implying statistical random distribution. However, the results of the study now show that the different reactions are not random, but that certain causes lead to predictable distribution patterns. The study has now been published in “Nature” and Pelkmans is glad to be reaping the first rewards for the research project, which was supported by ETH Zürich to the sum of 1.8 million Swiss Francs.

“For the project, we created an automated setup, the RNAi image-based screening centre, which we used to carry out a high turnover of cell experiments”, Pelkmans explains. The computer-supported methods were developed in conjunction with the experiments and allow the phenotypes of the cells to be quantified and described automatically. The data is fed into models and used to show how individual cell properties develop and affect each other.

The scientists focused their study on the cell properties predetermined by the population of the cell culture. This includes, for example, the size of the population, the local cell density, the size of an individual cell, whether the cell is on the edge of the cell culture and therefore not limited by another cell on one side, whether the cell is in the process of duplicating its nucleus (mitosis) or whether it is in the process of so-called programmed cell death.

Collecting large volumes of data

For each cell, the scientists examined the variety in endocytosis activity, by which cells invaginate parts of its biological membrane and absorbs the surrounding medium. They further looked at the variable amounts of a certain fat molecule (sphingolipid) on the surface of the cell, which plays an important role in relaying the cell’s signals and reactions. They also infected the cell culture with three different viruses and observed the differences in progression of the infection.

“We created a multivariable analysis of individual cells and obtained a very large number of very different readings”, Pelkmans explains. With this huge volume of data, the researchers used computer models to determine which variables affect each other. This allowed them to establish many rules, coined “heterogeneity signatures” by the scientists, which describe the way in which population-dependant properties of a cell culture influence cell reactions in the models.

Properties of the cell cultures determine variability

As the next step, the scientists tested how well the models would be able to predict the reactions of the cell. It was shown that this is possible with a high degree of accuracy and that the variability is clearly determined by the properties of the cell population. The cell cultures are naturally different from one another, explaining the broad variation in reactions of individual cells in the respective cell cultures during endocytosis and viral infections. For example, endocytosis is more uniform and is easier to control when the cell culture is densely populated, and certain diarrhoea-causing viruses can infect a less densely populated cell area more easily.

The findings are of particular significance for research using comparative cell cultures: “This is one of the most important methods, but at the same time also one that poses big problems for cell biologists”, says Pelkmans. The study has shown that reactions in two cell cultures can be better compared when the models to predict these reactions in each cell culture are used as a reference, taking into account the effect of the properties of a cell population of at least ten thousand cells. This is an important aspect, for example, for the pharmaceutical industry. As the study shows, many changes do not directly influence the cell, but the population as a whole, which then leads to changes in behaviour of individual cells.

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The Mating Game is a Team Sport

Are you looking for love but having trouble convincing the target of your infatuation to take you seriously? Or maybe hoping that certain unsavory types will stop looking for love with you? Well I'd recommend maybe updating your wardrobe and not hanging out in seedy bars by yourself anymore, but you might also be interested in new research suggesting that a important means of achieving your romantic goals involves less about what you do or where you do it, and more about who you do it with. That is, social coordination can improve your love life, whether that means finding the right person or avoiding the wrong one.

The idea that other people often factor into our search for romance is not new. Overbearing parents and desirable-but-pompous peers are two classic archetypes of history, literature and Hollywood movies (think Egeus in A Midsummer Night's Dream or Iceman in Top Gun). In scientific research, the role these other people play has by and large been restricted to competition. If you're a guy, other men represent people to trump in status or best in fights. If you're a girl, being more attractive or popular than other women is the name of the game. However, this other-people-as-competition framework misses a huge chunk of how we interact socially within romantic situations. We also: talk about potential romantic partners with people, find people to date by socially networking, and even directly help each other perform better on the mating market. You've probably done such things with your friends and family members. You may even have actively refrained from competing over the same guy or girl. These more cooperative forms of courtship behavior emerge through successful coordination of our own romantic interests with the interests of people with whom we share close, platonic relationships.

These behaviors may be immediately familiar, but research is now examining the evolutionary basis for "cooperative courtship" and identifying its differential appeal for women and men. Evolutionarily, the mating behavior of males and females (in all species) tends to be influenced by the physical and resource-based costs of pregnancy. Pregnancy is expensive, on the body as well as the pocketbook. The biological sex that spends the most effort gestating and rearing kids has the most to invest, and thus tends to be the most picky about choosing romantic partners (i.e., if you have to pay the cost, make sure to get a good deal). In many animals, including people, females are relatively more choosy. When it comes to cooperative courtship, therefore, females help each other to evaluate potential mates and avoid mates who don't make the grade. Males, on the other hand, tend to help each other get chosen. We see evidence for these strategies in animals, as when male turkeys help each other attract mates and when female bonobo chimpanzees form alliances to reduce sexual coercion.

People use very similar strategies, even though birth control has lowered the actual chance of unintended pregnancy. With my colleague Douglas Kenrick, I conducted several studies looking at how people coordinate their romantic interests. In one study, we showed people drawings of flirtatious scenes (see one in the image below) and asked them to identify who was a woman and who was a man.

Who would you guess? In other studies, we asked people about what kind of help people give to their friends and what kind of help they want to receive. We consistently found that everyone wants to help-competition is not the inevitable outcome. And though everyone helped in multiple ways, we found that women tended to help their friends build romantic barriers (weeding out the undesirable guys and testing the desirable ones), and men tended to help their friends break down those barriers (attempting to counter women's strategies). People used all sorts of techniques to do this, including having friends pose as counterfeit romantic partners (this worked for women AND men). Not only that, people also switched the kind of help they gave to their opposite-sex friends-now men helped women build barriers and women helped men break down barriers.

We even set up a Dating Game experiment in which people came to the lab expecting to be a contestant on a game show. The show wasn't all about competition though. At one point in the game, contestants had the option to act cooperatively with other contestants. Interestingly, in this "real-world" environment, women still gave more help when the potential date was an undesirable guy (suggesting barrier-building) and men still gave more help when the potential date was a desirable woman (suggesting barrier-breaking). We concluded that many of the romantic behaviors we think of as unique to our time and culture actually have their roots in universal biological principles.

There is still a lot of research to be done. I'd love to hear from people who have observed cooperative courtship in other cultures. Not all of the behaviors I mentioned will be cross-culturally identical, but I expect that people everywhere are helping each other achieve their romantic goals (e.g., in some cultures, family might provide more help than friends). I also think these findings are interesting because of their implications for cooperation in other contexts. For instance, how do people cooperate in business negotiations or in non-romantic social networking, and might women and men be better at certain negotiation and networking strategies than at others? Leave some comments below and let me know your thoughts.

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Scientists Develop Nasal Spray That Improves Memory

Good news for procrastinating students: a nasal spray developed by a team of German scientists promises to give late night cram sessions a major boost, if a good night's sleep follows. (Credit: iStockphoto/Ana Blazic)

Good news for procrastinating students: a nasal spray developed by a team of German scientists promises to give late night cram sessions a major boost, if a good night's sleep follows. In a research report featured as the cover story of the October 2009 print issue of The FASEB Journal, these scientists show that a molecule from the body's immune system (interleukin-6) when administered through the nose helps the brain retain emotional and procedural memories during REM sleep.

"Sleep to remember, a dream or reality?" said Lisa Marshall, co-author of the study, from the Department of Neuroendocrinology at the University of Lubeck in Germany. "Here, we provide the first evidence that the immunoregulatory signal interleukin-6 plays a beneficial role in sleep-dependent formation of long-term memory in humans."

To make this discovery, Marshall and colleagues had 17 healthy young men spend two nights in the laboratory. On each night after reading either an emotional or neutral short story, they sprayed a fluid into their nostrils which contained either interleukin-6 or a placebo fluid. The subsequent sleep and brain electric activity was monitored throughout the night. The next morning subjects wrote down as many words as they could remember from each of the two stories. Those who received the dose of IL-6 could remember more words.

"If a nasal spray can improve memory, perhaps we're on our way to giving some folks a whiff of common sense, such as accepting the realities of evolution," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "This is exciting piece of interdisciplinary science, since IL-6 had previously been considered a by-product of inflammation, not an agent that affects cognition."

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