Seeds of change?

Plant science is probably one of the least appreciated fields of life sciences, and yet, perhaps no other research area has produced as many technological advances beneficial for society. In an open letter released last month, 21 out of the 27 most cited plant scientists in Europe pledged decision makers to back plant research, which they feel is currently threatened by lack of funding and global public and political opposition to genetically modified organisms (GMOs).

“In comparison for instance with biomedicine and fields with technical applications, plant science is not well funded, and that’s particularly true when it comes to funding from Horizon 2020”, says Stefan Jansson of Umea University (Sweden), who coordinated the letter.

Credit: © chaiyon021 - Fotolia.com

In the open letter the scientists recall the fundamental role of curiosity-driven plant research for a sustainable society and to “deepen our understanding of nature”, and they warn decision makers that without their support—financial and political—the Horizon2020 goals to “tackle societal challenges” and “to ensure Europe produces world-class science” will not be met.  

Besides asking for funding to be maintained or, if possible, increased, they demand that plant scientists must be allowed to perform field experiments with GM plant varieties, and that Europe must “promptly” authorise new GM crops that have been found safe by the European Food Safe Authority (EFSA).

They claim that in most European countries, “permits to perform field experiments with transgenic plants are blocked, not on scientific but on political grounds”. And the few field experiments that do go ahead are often vandalised, wasting years of work and public funding.  To make matters worse, the scientists say in the letter, the ongoing de facto ban on approvals for new GM plant varieties in Europe has not only been damaging for applied plant science, but it has also increased the competitive advantage of agrochemical corporation giants like Monsanto; publicly funded scientists and small companies just don’t have the means to go through expensive, and sometimes decade-long, approval procedures.

“Every approval of a [GM plant] variety is enormously expensive, complicated and unpredictable, so no one ever tries nowadays”, says Jansson.

GMOs in Europe

This opposition to GMOs can safely be called epidemic. Lobbying by environmentalists and widespread popular resistance to GMOs has held back the use of GM plants in agriculture globally, but only in Europe the situation seems hopeless. A single GM plant is currently commercially cultivated in the EU— the MON810 maze produced by Monsanto that carries resistance to European corn borer, and which is cultivated in Spain, Portugal, Czech Republic, Romania and Slovakia. A de facto ban on GMO approvals has kept GM plants off the fields and out of our fridges for over 10 years. Environmental activists often associate GM crops with the ‘big bad wolf’ agrochemical companies, but in fact Monsanto and Syngenta have pulled out from the European market all together, so effectively the only people affected by this ban are farmers and plant scientists.

(March agains Monsanto, Vancouver, Canada, 2013. Credit: wikipedia)

“European agriculture is lagging behind when it comes to development, yields and so on. So every year the rest of the world is improving more than we’re doing here”, Jansson says “Unfortunately it’s because we’re not allowed to use the right technologies”.

The extreme position of France

This anti-GMO fever has changed the face of plant research in some European countries. France is an extreme example. It’s a national joke in France to say that all political parties, from far left to far right, agree on one thing: they’re religiously against GMOs. 

The radical resistance to GMOs in France began in the late 1990s amidst a growing anti-GMO mood that was quickly spreading worldwide. Ironically, back in those days France was at the forefront of the plant biotechnology field, and large consortium initiatives such as GENIUS and GISBiotechnologiesVertes (formerly known as Génoplante) received generous public funding. In fact, the first ever field experiment with a GM plant variety was performed in France in 1986, and for a decade, France ranked second only to the United States in the number of these experiments with GM crops, and they triggered no public protests. However, in just a few years the number of field trials in France plunged from over a thousand (in 1998) to only 48 (in 2004), and over half of these were eventually destroyed by activists. So what happened?

As the mad-cow disease and beef hormones scandals shocked the world in the mid 1990s, people began to become very sensitive about what was in their food. And exactly around this time, the Monsanto’s Roundup Ready soybeans controversy exploded. Not surprisingly, this promising new GM technology didn’t go down that well with the public. As Greenpeace promptly launched its first campaign against GMOs in 1996, a very influential French environmental activist named José Bové started a strong anti-GMO movement that conquered the French public opinion: from Parisian “bobos”, to journalists and even scientists, everyone seemed to hate GMOs, and politicians just followed the trend. 

The French Environmental Minister at the time, Corinne Lepage, began introducing laws to ban cultivation of GM plant varieties, and all subsequent governments, regardless of their political views, continued this anti-GMO policy. Activists that destroyed GM crops and research labs were prosecuted but got away with light sentences or amnesties. For instance, in 1999 protesters led by Bové completely destroyed a greenhouse for experiments with GM plants at CIRAD, a research centre for agriculture and sustained development in Montpellier. After a long and highly publicised trial, Bové was prosecuted to 6-months in jail, but the then president Jacques Chirac eventually “pardoned” four months of that sentence.

“They [the activists] are protected by the justice, they’re not really condemned. The laws were relaxed by the courts. It’s easier for these persons to get a meeting with the Minister of Research than for scientists,” says Georges Pelletier, president of the Scientific Committee of the French Association of Plant Biotechnology and former head of the Department of Plant Physiology of INRA (French National Institute for Agricultural Research).

Because of this strong public aversion to GMOs, and of the heavy administrative burden and expensive greenhouses required for testing GM varieties for agriculture, plant scientists in France have dropped their arms and simply “lost hope”, says Pelletier. Now, they use GM technologies only for basic research, and then adopt classical breeding methods to obtain the desired plant variety, or otherwise they perform field experiments with GM plants abroad.

“Nobody is growing GM crops outside anymore, after a while you understand the message”, says Brigitte Courtois, a researcher at CIRAD who is trying to obtain rice plants resistant to flooding by classical breeding, and who got some of her plants destroyed by Bové. “My main worry is that one day we’ll not be able to do any breeding because of this narrow vision.”

CIRAD and INRA, the largest public agricultural research institutions in France, have reduced the use of GM technologies in applied plant research to nearly zero. Once a leading country in plant biotechnology, France plant scientists in public institutions are now forced to work almost exclusively on fundamental research.

“The pressure on the scientists continues […] so in a way these people are also more or less destroying the science. They put pressure on the scientists hoping they will change their research”, Pelletier says.

Communication breakdown

(Credit: Acrylic Artist/Morguefile.com)

Since Monsanto’s Roundup Ready soybean scandal, activists don’t seem to be able to distinguish the agro-industry sharks from applied plant research, or in fact any plant research, so public and political resistance to plant biotechnology and innovation persists, and plant scientists suffer the collateral damage.

“I have stopped talking about [my work] with my friends. Even educated friends with the same background in agronomy, they all feel that there are other options, like organic farming […]. For me this is associated with the fact that people have no contact with agriculture anymore, they’re urban people who know nothing about how to grow a plant”, says Courtois.

But in other countries, there are some signs that if the public does listen to the researchers, they are more positive about the use of GM technology to tackle societal problems. At Rothamsted Research (UK), one of the world’s oldest agricultural research institutions, extensive information about their field experiments with GMOs is available online, and researchers make an effort to engage with the public to explain their research. The results start to show: while a couple of years ago protesters attacked (but not destroyed) a GM field trial at Rothamsted, the ongoing field experiment with Camina plants that produce omega-3 oils hasn’t been at all targeted.

“When we discuss our work with the public the general feedback is that the people are interested in what we are doing and more positive towards the use of GM technology in trying to address research questions and provide potential solutions to agriculture and food production challenges”, said Rothamsted’s researchers in a statement to Lab Times.

It is difficult though for plant scientists to get the message across to the public; if they’re not allowed to cultivate GM plants, how can they show their benefits for agriculture and society? And if the public doesn’t see those advantages, the lobbyists continue to put pressure on politicians to ban GMOs. It’s a vicious circle.

“All the new environment-friendly varieties that actually have been produced over the years, if they’re just in the drawers of the scientists and never been used in practical agriculture, then its much harder to convince society about the value of what we’re doing,” says Jansson.

Politics vs science

The date for the release of the open letter, at the end of October, was chosen carefully. The new European Commissioner for Public Heath and Food Safety, Vytenis Andriukaitis, took office on the 1^st of November, and just a few days later the European Parliament voted on a Commission’s proposal to give power to individual member states (MS) to ban GMOs in their territory.

This proposal was initially meant to be a compromise to unblock the over 10-year-long gridlock on GMO authorisations. Currently, any GMO approval in the European Union (EU) first needs to go through a thorough science-based evaluation by EFSA, and then the Commission drafts a proposal to either ban or authorise the new GMO according to EFSA’s recommendation. The proposal finally goes to the Standing Commission—made of politicians representing EU governments and public authorities—and they have the final say. If nine or more countries are against the Commission’s proposal, the approval is blocked. This has happened systematically for over a decade.

“When it comes to pharmaceutical industries, for instance, it’s not the politicians that make the evaluations whether the drug is dangerous or has side-effects or not, it’s the scientific body that does that”, says Jansson.

Anti-GMO countries like France have stalled the system by using spurious scientific arguments to ban GMO approvals, and applicants are either forced to spend years on end doing more and more safety tests, or they have to go into long and expensive legal battles to overturn the Commission’s decision (or lack of thereof). Inevitably, companies trying to commercialise their GM plant variety in Europe give up, while publicly funded researchers don’t even try.

This de facto ban has worked well for anti-GMO countries so far, but ironically, because of the countless scientific studies they’ve imposed, a huge amount of scientific evidence has accumulated showing that GMOs don’t pose any risk for human health or the environment. Anti-GMO countries are running out of arguments.

As a result, in an unprecedented move, thirteen countries formally asked the Commission to give MS the “flexibility” to ban EU-authorised GMO crops in their territory. Even though this would in theory go against the single market principle, in June 2014 the Commission approved a compromise proposal granting that request, but preventing MS from banning EU-authorised crops based on health or environmental grounds. This was a painful and much-negotiated compromise that could have worked. However, amendments introduced to the proposal by lobbyists will effectively give countries legal grounds to ban GMOs on reasons such as “environmental policy, town and country planning, land use, agricultural policy, public policy, or possible socio-economic impacts, GMO contamination of other products, persistent scientific uncertainty, development of pesticide resistance amongst weeds and pests, invasiveness, the persistence of a GMO variety in the environment or a lack of data on the potential negative impacts of a variety”, MEPs say in a press release. So pretty much any reason will do.

The Commission’s amended proposal was approved by the European Parliament in November. The decision is not final yet, but the future for GMOs in Europe seems bleak.

“The amendments that give MS the ability to challenge cultivation on grounds of safety are worrying because they undermine the risk assessment performed by EFSA” Rothamsted researchers voice their concern in a statement to Lab Times. “Potentially, it will also make it harder for MS who do not want to opt-out to justify to their consumers when neighbouring MS are using safety as a reason to ban”.

The worry is that pro-GMO countries won’t be able to cultivate EU-authorised GM crops in their country because activists can now say “If that country banned this crop on safety grounds, it must mean it’s unsafe”, and this will put even more pressure on politicians to ban GMOs. EFSA’s science-based evaluation will lose weight on GMO approvals; the power will lie merely on politicians, and science will have little impact on future decisions to authorise or ban GM crops in Europe.

Seeds for the future

The open letter has so far not received any response from the European Commissioner, but it got extensive media coverage and excellent feedback from the research community, except in France, where researchers seem to prefer to remain quiet.

“The letter was addressed to two French scientists amongst the best in Europe and they didn’t want to sign. One of them because of the question of GMOs and application was inserted in the letter, so he didn’t want to sign. The other never replied”, reveals Pelletier.

So what’s the future for plant science in Europe?

Jansson says “It won’t disappear but it won’t flourish either. Maybe, in 10 years, there will be fewer plant scientists and they will be a little less useful for society.”

Reference:

Bonneuil C. & C. Marris (2007). Disentrenching Experiment: The Construction of GM--Crop Field Trials As a Social Problem, Science, Technology , 33 (2) 201-229. DOI: http://dx.doi.org/10.1177/0162243907311263

This article was published in Lab Times on the 9-12-2014. You can read it here.

Turning on proteins with light

Just like for married couples, communication is fundamental for cells. When an embryo is developing, its cells need to tell one another who and where they are, so every tissue and organ grows in the right place and at the right time. Our neurons are constantly talking to each other to control our thoughts, feelings and behaviours. Even single-cell organisms like bacteria can exchange information to decide, for example, how many times they should multiply.

But how do cells communicate? Scientists have a good understanding of the key proteins involved in cell communication, or cell signalling. Typically, a cell sends out a chemical signal (or electrical, in the case of neurons) that sticks to a specific receptor protein on the surface of the neighbouring cells. We then say the receptor is ‘activated’, because it can trigger a cascade of molecular events that ultimately leads to a cellular response. For instance, the cell might start moving in a particular direction, or a specific gene gets translated into protein.

There is, however, quite a lot we still don’t know about cell signalling. What would happen if we could activate a receptor only at the tip of a moving cell? Would the cell change the direction of migration? And what if we could activate a receptor repeatedly, or at different time intervals? Would the cell responses be different? Questions like these have been bugging scientists for decades, but they simply lacked the tools to address them.

Now, a research team led by Harald Janovjak at the Institute of Science and Technology (Austria) has developed a new method to study the fine temporal and spatial regulation of cell signalling using proteins activated by light. This work opens the way for the development of powerful approaches to manipulate cell behaviour in health and disease.

Human cells illuminated in a pattern depicting the letters IST. The cells carry a reporter gene that 'glows' when it is triggered 
with light-activated receptor tyrosine kinases (Credit: Medical University of Vienna).

The optogenetics revolution

Scientists have been using engineered light-activated proteins to manipulate cell activity for about a decade or so, a technique that has been named ‘optogenetics’. The first light-activated proteins, or photoreceptors, applied in optogenetics belonged to the microbial opsin family. These opsin photoreceptors are useful because they can move ions across cell membranes in response to light, a process similar to what triggers neuron activation. In these initial studies, channelrhodopsins (a type of opsin photoreceptor) were removed from algae and inserted into particular neuronal cell types in mice. Upon exposure to light, the neurons containing these proteins started to fire, and depending on which neurons were activated in this way, a different behaviour was observed in the mice; in one study, the mice’s levels of anxiety increased, and in another they started going round in circles.

The reason why optogenetics has been coined a ‘revolutionary technique’ (and why it is tipped for a Nobel prize) is that it allows scientists to control the activity of particular cell types or proteins with an unprecedented level of precision, both in a temporal and spatial manner. And this, sure enough, comes very handy for cell signalling research. It is a bit complicated though, to build optogenetic tools for that purpose.

“The main challenges are the same as for many engineering problems. For example, you want the signalling receptor to be completely inactive in the “OFF” condition (no light), and to be as much active as if the natural chemical signal is added in the “ON” condition (light),” says Janovjak.

This fine level of receptor manipulation is very hard to achieve with conventional optogenetics tools, so Janovjak and colleagues decided to build signalling receptors activated by light from scratch, by taking bits and pieces from several proteins and then sticking them together.

They focused on cell-surface receptors of the receptor tyrosine kinase (RTK) family, which sense growth factors and hormones and have been involved in a variety of cellular processes. When an RTK receptor is activated by a chemical signal, let’s say a growth factor, it attaches to another receptor in what is called ‘dimerisation’. It is this contact between two RTK receptor molecules that triggers the molecular events leading to a cell response, or in other words, that activates RTK signalling. Janovjak and colleagues knew this, so they looked in bacteria, fungi and plants for proteins that dimerise in response to light, and then fused them to an RTK receptor skeleton. In theory, these engineered RTK receptors should dimerise—and therefore become activated—upon light exposure.

“We were quite beautifully able to do this. In our study cancer cells with RTKs under optical control quantitatively respond to light and the growth factor! This is nothing short of amazing and the basis for all future work by us and others,” says Janovjak.

Manipulating cell signalling with light

The team showed that when engineered RTKs are inserted into several cell types, including cancer cells, they can be efficiently activated by light and induce the predicted cell response very quickly and within a tiny spatial range.

Morgan Huse, an expert on cell signalling at the Sloan Kettering Institute (US) says “This study represents the first time that homodimerising [light-activated] protein domains have been used to activate RTK signalling. The results are quite significant.”

These new optogenetic tools will be invaluable for understanding cell signalling, and could also be adapted to study other cellular processes. In the future, Janovjak’s team will use these tools to investigate regeneration.

“Our research will focus on regeneration. In essence, growth factors are known to be efficacious in disease animal models, including diabetes and Parkinson’s disease. However, delivery of these growth factors is a real issue because they can induce side effects like (but not limited to) cancer, and growth factors often can’t reach the desired cells (for example in the brain). Maybe optogenetics can help”.

Reference:

Grusch M., R. Riedler, E. Reichhart, C. Differ, W. Berger, A. Ingles-Prieto; H. Janovjak (2014). Spatio-temporally precise activation of engineered receptor tyrosine kinases by light, The EMBO Journal, 33 (15) 1713-1726. DOI: http://dx.doi.org/10.15252/embj.201387695

This article was published in Lab Times on the 22-08-2014. You can read it here. 

Interview with Nobel laureate Sir Tim Hunt

I recently spoke with Nobel laureate Sir Tim Hunt about the current research scene in Europe in an interview for Lab Times. We discussed topics such as research funding, gender inequality in academia and the publishing system. Below is a summary of his career and the full interview.

Sir Tim Hunt started his research career in 1964 at the University of Cambridge (UK) working on haemoglobulin synthesis under the supervision of Asher Korner. After obtaining his PhD in 1968, he spent a few years at the Albert Einstein College of Medicine in New York (US) working with Irving London, until he returned to Cambridge to teach and establish his independent research career studying translational control. In the late 1970s, he began teaching a summer course at the Marine Biological Laboratory, Woods Hole (US), where he began working with sea urchin and clam eggs. These experiments eventually led to the discovery of cyclins, a family of regulatory proteins that partner with cyclin-depent kinases (CDKs) to control the transition between cell cycle phases. For this breakthrough Hunt was awarded the Nobel Prize in Physiology or Medicine in 2001, together with Lee Hartwell and Paul Nurse for their work on CDKs in yeast. In 1990, Hunt moved his laboratory to the Clare Hall Laboratories at Imperial Cancer Research Fund (now London Research Institute/Cancer Research UK) where he carried out pioneering research on cyclins and cell cycle control until his recent retirement. He is a former Chair of the European Molecular Biology Organisation (EMBO) council, and currently member of the Scientific Council of the European Research Council (ERC), the Advisory Council for the Campaign for Science and Engineering (CaSE) and of the Selection Committee for the Shaw Prize in Life Science and Medicine.

You have recently retired from a long and prolific research career. How different is it to pursue a research career now, compared to when you started, or even just a couple of decades ago?

Hunt: I always like to joke that I am glad that I am not 20 something years old today, because I think it is much harder than when we started. When I started as a PhD student in 1964 our department didn’t have a Xerox machine, there were no calculators, you had to go to the library to read things and it was virtually impossible to analyse individual proteins because the SDS gel had not yet been invented. The tools were very blunt and the questions you could ask were corresponding limited; now the two are exceedingly sharp and the analytical procedures are absolutely awesome. […] When you look back at the papers of that era they were pretty simple, easier to understand in many cases. There was only so much you could do. I am appalled sometimes at some papers today; they are so data heavy, and I don’t think that makes them better papers. […] In terms of publication there is just much more competition these days, because the biosciences have been so successful; they consume about 2% of the growth national product in the US and the result is that there are thousands of competing young scientists. My generation is just on the point of retirement, and in the meantime we have all trained dozens of doctoral students and postdocs, each of which has trained their own students and postdocs, so this exponential growth is what caused all the problems, I would say.

And where do you think all this is heading?

Hunt: I really don’t know… Somewhere between 1990 and 2000 many of the outstanding problems of cellular, molecular and developmental biology were effectively solved. You do kind of wonder: how many really important problems are there in biology that remain? Of course there are hundreds of details but the last great frontier is how the brain works, there you have a very primitive partial understand of most of it. […] It is a pretty difficult problem.

Is the European Union currently taking the right measures to move European science forward?

Hunt: The old investigator-led grants are excellent and much better that top-down collaborative network grants, which are quite good fun but I don’t think it is a terribly good mechanism to hunt for the best science because the people aren’t really working together. When you really work with somebody you see them everyday, and here the idea is that you see one another once a year, or perhaps four times a year, it just doesn’t work. There are projects that might work, like these huge projects to sequence the human genome, the big science, but mostly I think that biology is still pretty small science that has to be carried out by committed individuals focusing on particular problems. I don’t know very many things that require that kind of effort.

What are the strengths and pitfalls of the European research community, when compared, for example, with research in the US?

Hunt: I think things have improved tremendously in Europe in the last few years. For example, in my field, the European Molecular Biology Laboratory (EMBL) has trained lots of people, not only in how to do science, but also on how to manage science and how to choose scientists. […] I believe very much in giving power to the young and not putting them under. I was given full autonomy and authority at a very young age, at 27 years old. I wasn’t running my own lab, I had friends around to help and I liked that. There is much more internationalization in Europe, good practice [of science] is much more diffused throughout. In the former communist countries, Poland, Bulgaria and places like that, they still have a long way to go but it is difficult to feed because any new talent that arises, very quickly migrates abroad. At the ERC we think about that a lot but we haven’t really taken steps to deal with it because it is against our principles. We say excellence only and that rules most of those people out, and it is understandable, they don’t have a good science base, and it is hard to see how they can build one.

What do you think of big science prizes like the Breakthrough Prize? Some people claim that junior scientists should receive this type of prize instead of established scientists. 

Hunt: I don’t know to be honest. You have to find a compromise. If you are a granting agency, you really do need to try to identify people who are successful and clever, and that will make good use of the money. There are a lot of funding agencies and in the past you feel that every person had to get a little piece of the cake, and in general, that meant that the food is spread too thinly. So I think that a bit of concentration is a good idea, but that then raises the question: how do you identify the good people? That is when the problems begin, because now we start talking about impact factor and things like that and everybody knows there are problems with that but nobody has found a satisfactory solution. We are good at judging science retrospectively but we are not good at judging science prospectively, because the future is always very hard to predict. The ERC does the best it can. We like to keep things very simple and in judging grant applications you give half the marks to track record of the applicant and half the marks to the project they propose. I think that is a pretty good ratio. You can’t just give money to people who have been successful in the past and say ‘do whatever you’d like’, I don’t think that sort of view is responsible although in some cases it will be fine. And likewise people can propose very fancy and clever research projects but when you look at their productivity you see that they are much better at writing grants than actually carrying out research. Somewhere between those two extremes lies the compromise.

How can we change the way scientists (and science) are perceived by the public?

Hunt: I don’t know, I think that is a very difficult question to answer. People always say that scientists must be encouraged to go out and explain what they are doing. I’m all for that, I try to do a little bit, I go and talk in schools and so forth. But nothing never really comes close to the experience of actually doing science, which is usually a rather peculiar random walk, mostly failure and the occasional few successes. But it doesn’t really explain why it is so wonderful and such good fun to do because in order to understand it you have to usually have first done a PhD in the subject and most people haven’t. I would find it difficult to explain to a quantum mechanics expert what I was doing and why I thought it was interesting. […] Science is really just a way of finding things out. You pursue a lot of false clues, you get misled and misinterpret things. And that is very hard to convey and unfortunately I think the teaching of science in school is very delusive…. They make it sound that there are some geniuses out there that figured everything out and then wrote it down in textbooks. And all you have to do is learn what it says in the textbooks and you will be a brilliant scientist, but we all know that textbooks are actually wrong in lots of places. And the alternative to that of course is: ok we won’t teach the kids what is known, we will let them find it all out for themselves. But if you have to find everything out for yourself it takes an awfully long time to discover anything. It is really important to have practical experience, but it is very difficult to give people practical experience of what it is really like to be pursuing a real live problem.

Do you think scientists are pressured to focus their research on ‘hot’ topics, like cancer or neuroscience?

Hunt: I think they are. It is the money issue; people tend to migrate in that direction because they have no choice. I don’t think it is a very sensible way to spend the money. I am a tremendous believer in fundamental research. When I look at the great breakthroughs, like the discovery of penicillin, that wasn’t produced by doctors wanting to make antibiotics, none of them realised it was possible. It was a tiny handful of basic researchers who were curious and figured out how to do it. I think this emphasis on translation research is very foolish, because it implies that we know everything that we need to know, and that is not true obviously. A good example is the case of gene therapy, which is much needed to treat genetic diseases and it doesn’t work very well because much more biological engineering is required. I think most biological fields are well populated, and if a breakthrough occurs they won’t fail to exploit them.

How would you explain to someone in one sentence that it is important to fund and encourage more basic research?

Hunt: I wouldn’t know how to begin! I think it is extremely difficult to justify because what you are really saying is ‘just pay me to have more fun’ and that works much better than paying me to do something I have no clue how to do.

In your opinion, why are women still under-represented in senior positions in academia and funding bodies? 

Hunt: I’m not sure there is really a problem actually. People just look at the statistics. I dare myself think there is any discrimination, either for or against men or women. I think people are really good at selecting good scientists but I must admit the inequalities in the outcomes, especially at the higher end, are quite staggering. And I have no idea what the reasons are. One should start asking why women being underrepresented in senior positions is such a big problem. Is this actually a bad thing? It is not immediately obvious for me that… is this bad for women? Or bad for science? Or bad for society? I don’t know, it clearly upsets people a lot.

What research area excites you at the moment?

Hunt: I am very excited by stem cell biology. I think the advances that have been made are just fantastic and I really hope that is something that will lead to people growing pancreas in a test tube and use them to cure diabetes, for example. I think that those advances have been absolutely spectacular, very, very interesting.

Interview by Isabel Torres

This interview was published in Lab Times on 4-07-2014 (print issue). 

Tun-ing in on water bears' superpowers

Water bears, or tardigrades, are harmless microscopic animals. Yet, despite their endearing bear-like appearance, tardigrades are the hardest animals to kill on Earth. And boy, many have tried.

Tardigrades are chubby eight-legged animals, no longer than the head of a pin, related to velvet worms and also arthropodes, a large family including insects, spiders and crustaceans. They can be found anywhere where there’s water, but they prefer to live in damp moss and lichens. These tough creatures can survive boiling temperatures up to 125˚C* and freezing temperatures so extreme (-272˚C!) they can only be artificially created in a laboratory. They can also survive astonishing amounts of radiation with no apparent damage to their DNA, extremely high pressures, and, unlike any other earthly creature, tardigrades can hang out for a few minutes in the vacuum of space and come back alive to tell the story.

Tardigrades (Hypsibius dujardini) imaged with a scanning electron microscope.

So what’s their secret? Tardigrades have the amazing ability to reversibly slow down their metabolism to nearly a halt (less than 0,01% of their normal metabolic rate) in response to a change in their environment—a process called cryptobiosis. Other organisms can do it—nematodes, rotifers, brine shrimp—but not nearly as spectacularly as tardigrades. It is estimated that they can lose up to 99% of their water content, and enter a so-called ‘tun’ stage that protects them against harsh environmental conditions. Yet, if you rehydrate these tuns, the animals will quickly return to their normal selves—moving about, growing and having babies, as you do when you’re a tardigrade (watch movie below).

Scientists grow tardigrades in the lab (and sometimes in space) to study cryptobiosis. Understanding how tardigrades survive extreme dehydration during the tun stage could help developing better techniques for dry preservation of biological material, for example.

In a recent study, Marcus Frohme and colleagues from the Technical University of Applied Sciences in Wildau (Germany) compared differences in gene expression between happy, dehydrating, tun stage and rehydrated tardigrades. The idea was to search for the genes that are more, or less active in each of these metabolic states, which could give some clues as to how the tardigrades’ cells cope with severe dehydration. The researchers grew four groups of animals in the lab under different conditions (from moist to dry) and then smashed them up to chemically extract mRNA molecules (copies of DNA that will be translated into proteins) from their cells. They then sequenced and quantified these molecules, and finally analysed the huge amount of data using a powerful computer software.

The team found that in the dehydration stages, genes involved in cell division and growth were less active, but genes encoding for proteins that protect or repair cellular components, such as heat-shock proteins, were highly expressed. These results confirm previous research, but some preliminary data in Frohme's study also suggest that several genes involved in DNA repair are more active in the rehydration stage than in the dehydration stage. The authors propose that tardigrades adopt a dual strategy combining mechanisms of protection (during dehydrating stages) and recovery (during rehydration stages) to survive desiccation.

* In the original article it was written 151˚C, this has been corrected to 125˚C (reference: Doyère P.L.N. Memoires sur les Tardigrades. Sur le facilité possedent les tardigardes, les rotifers, les anguilleles des toit et quelques autres animacules, de renvenir à la vie après été complement désesschées. Ann. Sci. Nat. 18: 5, 1842.)

Reference:

Wang C., Grohme M.A., Mali B., Schill R.O., Frohme M. & Gibas C. (2014). Towards Decrypting Cryptobiosis—Analyzing Anhydrobiosis in the Tardigrade Milnesium tardigradum Using Transcriptome Sequencing, PLoS ONE, 9 (3) e92663. DOI: 10.1371/journal.pone.0092663.s006

A shorter version of this article was published in the print issue of Lab Times on the 13-05-2014.

All eyes on bioprinting

3D printing is in fashion. Clothes, prosthetic limbs, guns and even pizza, you name it—just about anything can be printed these days. Even living cells.

Bioprinting is an emerging technology that promises to revolutionise the field of regenerative medicine. The idea is simple: you load a printer cartridge with cells removed from a patient or grown in the lab, and then print a brand new tissue or organ ready for transplantation. Alternatively, you could print healthy tissue directly onto a patient’s wound in the operating room. For now, scientists and biotech companies have managed to print several cell types, and there has been some progress in making cartilage, skin and heart muscle tissue. Printed tissues like these could be invaluable for drug testing in preclinical studies and for regenerative medicine. Imagine if we could replace damaged brain tissue in people suffering from neurodegenerative diseases like Alzheimers, or treat blindness with transplanted eye tissue. But how does bioprinting work?

By a lucky coincidence, the size of the nozzles of inkjet printers is roughly the same of an average animal cell, so scientists can use or adapt commercial printers for bioprinting. Just like a conventional 3D printer, which creates objects by laying down liquefied material (like plastic, metal or even chocolate) in layers, bioprinters work by spitting out cell after cell onto a surface to, in theory, build a 3D-shaped living tissue. But there is a caveat. Some cells are not happy to be squeezed through a printhead, like neural cells for example, which have a limited ability to survive and grow in culture. 

Now, researchers from the University of Cambridge (UK) report that they have successfully printed two types of rat neural cells from the retina, the light-sensitive tissue at the back of the eye: ganglion cells, which transmit visual information to the brain, and glial cells, which insulate, support, protect and feed neurons.

Barbara Lorber and colleagues pushed a gel containing the cells through a piezoelectric inkjet printer and then tried to grow them in culture to test their survival rate. Piezoelectric printers are not commonly used for bioprinting because they use an electrical pulse to eject the ink drops, and this was thought to break cell membranes. But this is not what the team found. The large majority of printed ganglion and glial cells were able to survive and grow in culture. They also seemed to retain their function—glial cells released growth-promoting molecules, and in turn ganglion cells responded to these signals by growing more of the tiny processes that carry messages to neurons.

In recent years, stem cells transplants and electronic retina implants were shown to partially restore sight in patients with retinal degeneration, but these improvements were modest. Although preliminary, the new results by the Cambridge team provide the proof-of-principle that the production of functional retinal tissue by bioprinting could one day become a reality.

Reference:

Lorber B., Hsiao W.K., Hutchings I.M. & Martin K.R. (2014). Adult rat retinal ganglion cells and glia can be printed by piezoelectric inkjet printing, Biofabrication, 6 (1) 015001. DOI: 10.1088/1758-5082/6/1/015001

This article was published in Lab Times on the 10-02-2014 (print). 

Image credit: namida K/Everystockphoto