By Miguel Ángel Sabadell
PACE project: creating life in the laboratory
Thelifetimeit is something as beautiful as it is enigmatic. All forms of life are made up of molecules that, in themselves, are not alive. How did this transition from inert matter to life take place? Leaving aside religious approaches – which all they do is replace the enigma with an even greater one – since the middle of the last century an attempt has been made to understand this central problem in biology.
At present, various research groups around the world are trying to answer how simple life forms can be manufactured in the laboratory: they are the so-calledartificial cells or protocells. It is thought that they will be totally different from any existing or extinct form of life, many times smaller than the smallest of bacteria and, of course, simpler: we try to understand life, not create Frankenstein.
One of the approaches isfrom “bottom up”: Starting with raw “molecular screws”, scientists try to make a “protocell” without frills, with everything that is strictly essential.
One of these ongoing projects is the EuropeanPACE(Programmable Artificial Cell Evolution), which brings together 13 European research groups, among which is the Complex Systems Laboratory of the Pompeu Fabra University of Barcelona, directed byRicard Solé. “The theoretical models as well as the experimental data give us good reasons to believe that we will be able to obtain simple protocells from a simple system of coupled reactions involving the essential components that make the basic characteristics of living units possible”, he explains. Solé, whose group tries to predict the dynamics of artificial protocells and their possible evolution.
Perhaps the best way to see these artificial cells is asnanorobots, which are now so fashionable in science fiction novels and films, working on a molecular scale: the result will be a hybrid technology, mixing biotechnology with nanoelectronics: “to create a new generation of computers and self-repairing robots, as well as to direct successfully any type of operation at the nanoscopic level, it is essential to buildself-organized intelligent systemsand capable of evolving in the right direction, such as programmable artificial cells. “They will integrate three microscopic biochemical systems: a container, which will perform the functions of cell membranes, a construction system (metabolism) and a genetic system, which store and manage information (DNA). With research like these we are a little closer to understanding life, its origin and evolution. The doors that this opens are immense. The problem is to know if we are going to measure up to if we will continue with the same mentality as in the Lower Palaeolithic.
Web: complex.upf.es/~ricard/PACEsite
Minimum genome: what do we need to live?
The sequencing ofhuman genomecaused some disappointment among scientists: the prediction that we had 100,000 genes was drastically reduced to about30.000. Faced with such a quantity, one may wonder: if an organism as complex as humans requires these few genes, how many require simpler organisms, such as bacteria? Even more, what is theminimum number of genes necessary for life?
This adventure was launched a few years agoCraig Venter, former director of Celera, the biotechnology company that recently managed to complete the sequence of the 3,000 million nucleotides that make up the human genome. It is part of his ambitious project to synthesize a living organism in the laboratory. To do this, Venter needs to identify the minimum number of genes that allow an organism to grow and reproduce autonomously.
Within this context, the Cavanilles Institute for Biodiversity and Evolutionary Biology of Valencia, in collaboration with other research centers in Spain, is sequencing the complete genome of insect endosymbiont bacteria, such asBuchnera aphidicola, which was completed a few years ago, being the first genome fully sequenced in Spain.
What is the peculiarity ofBuchneraWhat makes it especially interesting in the field of study of minimal genomes?Buchnerais directly related to the well-known bacteriumEscherichia coli, common organism of the human intestine and model system in bacterial genetic research; but unlike this one,Buchnerahas undergone an evolution due to the reduction of its genetic material, reaching a genomic size almost eight times smaller than that ofE. Coli, which makes it one of the smallest known genomic bacteria.
This minimal genome is a consequence of the life system ofBuchnera, adapted to living insymbiosisinside specialized cells of various species of aphids. The symbiotic relationship is so close that currently neither of the two organisms can live without the other. Adaptation to the intracellular life system inBuchneraIt is reflected in its genome, as can be deduced from this study: those genes responsible for expendable cellular functions in the protected environment inside the aphid were eliminated over time.
With this type of work it is possible not only to delimit the minimum genome necessary for an intracellular life system, but also to know how these bacteria are integrated into the insect-host.
Web: www.uv.es/~biodiver/c/inve/grup_gen_evolut.htm
Studying the oldest light in the Cosmos
More than 75 years agoEdwin Hubblediscovered theexpansion of the universe. Actually, what he found with his telescope on Mount Wilson (California) is that the light coming from the galaxies is shifted towards the red in the same way that the horn of a car seems more serious when it moves away from us. And that happens whether we observe from Earth or from any planet located in any galaxy. This surprising observation was interpreted as that the entire universe expands in the same way as a raisin cake or a globe that we have painted with a marker on its surface. Neither the raisins nor the dots (the galaxies) move; the cake dough grows or the balloon rubber (space-time) stretches.
If the universe originated with a formidable explosion, is it not possible that we can still hear an echo of that? This is how Princeton cosmologist Robert H. Dicke thought in the early 1960s. He believed that there must be some kind of residual radiation left and proposed to one of his researchers, Jim Peebles, that he start to calculate what would happen if the universe had really been born in this way. And he found that today we would have to see a microwave background covering all of space, something that had already been predicted 10 years earlier by the father of the Big Bang, the Ukrainian George Gamow, and that had fallen into oblivion. Curiously, this background was being observed and it was leading two radio astronomers from the Bell company, Arno Penzias and Robert Wilson. Iscosmic background radiationIt comes from when the universe was 300,000 years old. Until that moment the history of the universe had been characterized by a boredom broken only by photons colliding with nuclei of hydrogen and helium and electrons: the universe was opaque to radiation. It was then that light stopped interacting with matter – the universe became transparent – and that light is what we see today in the form of microwave radiation that floods the cosmos. This is the oldest light that we can observe and marks the beginning of what has been called theDark Age of the universe.
Was theCOBE satellitewho announced to cosmologists that background radiation was distributed extremely evenly through space, but not perfectly uniform. There were fluctuations, on the order of one part per 100,000; minimal but decisive for the future of the universe. Because thanks to them the first structures of what is now our universe could appear: galaxies, clusters and superclusters owe their existence to these minute variations, of which no one yet knows what they were due to. Determining with the greatest possible sensitivity the value of these background radiation anisotropies is one of the objectives of this research program developed at the Instituto de Astrofísica de Canarias directed byRafael Rebolo, to be able to limit the value of the most relevant cosmological parameters, such as the densities of ordinary matter, dark matter and dark energy, the mass of the neutrino, the expansion or Hubble constant …
Web: www.iac.es/project/cmb/index_esp.php
Diseases of the second genome of the cell
All our cells havetwo genetic systems. One is well known to all: it is found in thecoreand encodes most of the cell’s proteins. The other is in themitochondriaAnd, although it encodes a small number of proteins, it is essential as it is responsible for the production of the energy necessary to live. Mitochondria are the cell’s lung, the place where the cell uses oxygen to carry out the chemical reactions that allow it to live. Its DNA was discovered in the late 1960s and in the early 1980s it became the first human genome to be fully described.
Who discovered its origin was the microbiologistLynn Margulis, known among those who are interested in scientific topics for two reasons: one social and the other researcher. The social is that she was married to the famous Carl Sagan. The scientific aspect is the one that is linked to the concept of symbiogenesis.
A few years ago Margulis had the happy idea of seriously raising that one of the engines of evolution is the symbiosis between species that are in contact. Symbiosis is nothing other than “collaboration”, said in quotation marks and with many qualifications, between two living beings of two different species because they mutually benefit in their struggle for survival. We have an example in lichens, a symbiosis of a fungus and an alga.
Margulis proposed that the mitochondrion was actually a bacterium that symbiotized in the early stages of life on Earth with primitive cells. The evidence on which he based this claim was to some extent circumstantial: mitochondria look like bacteria and have different DNA from the cell in which they are found. Today we know that he was right: they are descendants of aerobic bacteria that were absorbed 1.5 billion years ago by the ancestors of our current cells. Thanks to this they acquired the ability to use oxygen to produce energy. Over time these primitive bacteria lost their autonomous ability to multiply and became dependent on the host cell. In the end, only the genes that encoded the proteins that participated in the production of cellular energy remained.
Mitochondrial DNA is about 3,000 times smaller than the smallest of chromosomes and contains information for 37 genes that lie one after the other with no gaps in between.
One of the most striking features of themitochondrial genetic system, the thing isis inherited exclusively from the mother. Women pass it on to all their sons, but only daughters will pass it on to the next generation.
In the Department of Biochemistry, Molecular and Cellular Biology of the Veterinary Faculty of the University of Zaragoza, Julio Montoya and his group investigate to understand the basic knowledge of the functioning of this genetic system and study mitochondrial diseases, a group of disorders caused by a defect in the production of cellular energy. These diseases, very devastating and difficult to identify, affect both children and adults and their diagnosis goes through genetic analysis. Only then can your palliative treatment be better decided.
Web: http://wwwbioq.unizar.es/anterior/departamento/investigacion/servicio%20diagnostico.htm
Green Chemistry
Green chemistry means reducing the environmental problems generated by chemical production without using end-of-pipe solutions, eliminating contamination, but tackling the root problem: using chemical processes that do not produce waste products.
In the early 1990s the EPA, the US environmental protection agency, coined the termGreen Chemistryin order to promote innovative chemical technologies that reduce the use or generation of hazardous chemical substances in the design, manufacture and use of chemical products. It can be considered the moment of starting this new way of doing chemistry.
It is curious to discover that the industry that we would all point to as the most polluting, the petrochemical industry, only generates about 0.1 kg of waste per kilo of product. And, curiously, the dirtiest is the one that seems cleanest, the pharmaceutical one: up to 100 kg of residue per kilo of useful product. That is why this is the field in which the greatest efforts are being made. Thus, the synthesis of the active ingredient in Viagra was one of the first pharmaceutical processes to incorporate green chemistry.
Within this philosophy is what is known asatomic economy: all the atoms that enter a reaction must appear in the product, without generating any by-products. For this, catalysts can be used, substances that serve to accelerate or improve the performance of the reaction at the same time as its energy consumption, but which do not disappear in the reaction.
This is one of the research fields of the Valencia Institute of Chemical Technology, where Avelino Corma’s group has developed a series ofgold-based catalystswhose use in obtaining anilines -vital for the pharmaceutical industry and obtaining herbicides and pigments- does not generate any residue. This result is tremendously important because the processes used so far have generated almost the same amount of waste as the desired product. In particular, the catalysts developed are based on gold nanoparticles and avoid the formation of other secondary products.
Web: : itq.webs.upv.es
Mars on Earth
In the Sierra de Huelva theTinto river. Its name comes from the red color of its waters, of marked acidity and high content of heavy metals, toxic to life, which are dissolved. As determined years ago by a group of biologists from the Autonomous University of Madrid led by Ricardo Amils, the main component present in water is iron. In fact, this river is characterized by its extreme acidity and a high saturation of iron and sulphates. In some cases, the measuring instruments used in the laboratory give values close to 20 grams per liter of iron concentration, that is, concentrations difficult to achieve in any other environment on the Earth’s surface. The high concentration of sulfates together with thehigh acidityof the river makes us imagine the river water as a sulfuric acid solution.
At first it was thought that nothing could live in such an environment, so he was believed dead. However, studies have shown that not only can life develop in these types of extreme environments, but it also has enormous biodiversity. Not only that, she is responsible for its peculiar characteristics.
Feeding thesemicroorganisms, calledchemilithotrophs, is carried out by oxidizing the iron of the pyrite in the subsoil, which gives the characteristic reddish color of the river. But the biggest surprise came when we discovered that not only extremophilic life forms are found there, but a much broader biological diversity. It has been found that a large part of the majority groups that make up the tree of life are represented: microorganisms belonging to the group of animals, plants, fungi …
The study of this ecosystem provides a great deal of information about the robustness of life and turns out to be asmall scale modelof the conditions that could be present in theplanet MarsIt is possible that iron was a predominant element in the chemistry of the first environments on its surface. The high availability of iron in the earth’s crust may have favored certain catalytic reactions that culminated in the prebiotic synthesis of the first organic molecules.
Web: www.cab.inta.es/
Seeds for eternity
The next time you go to the market, stop for a moment at the grocery store and count the types of lettuce you see; they sure don’t go beyond five. Did you know that the Germplasm Bank of the Aragonese Agrifood Research and Technology Center conserves seeds of more than 800 different lettuces? Or 3,000 different peppers? There are not only those of the piquillo …
AGermoplasm Bankit serves the same purpose as a human sperm bank: storing genes. Of course, the objective is quite different, and not only for the interest of the second to do business. The mission of a horticultural bank is to create a source of genetic variability for the improvement of agriculture in the not too distant future. We are talking about research, not about a seed house.
Spain has several banks spread over the different autonomous communities. Perfectly coordinated and organized, the leadership of all of them is rotating, the three most important in the country being that of the Polytechnic University of Valencia, that of Madrid (where the national bank is located), and that of Aragonese. These banks hold tens of thousands of different seeds. And they are always on the rise.
Prospecting, multiplying, evaluating and conserving. This is the motto of any genebank. The technicians, true Indiana Jones of seeds, look for contacts between the agents of nature protection and people linked to the world of agriculture … Although it is normal for the farmer to buy the seeds, sometimes it can be found that he has a onion, a tomato or a parsley that his grandmother already grew. Then they ask for a few seeds. Back at the bank, it is cultivated – technically said, multiplied – so that for each gram of seed you get 300. Nobody dies if someone remembers you and that melon that a family has cultivated with care forever will not be lost. The germplasm banks collect that seed that has been in the village for hundreds of years to preserve it.
But not only useful plants for man are sought. The Germplasm Bank of the Botanical Garden of the University of Valencia also preserves the endemic, rare or threatened species of the flora of the western Mediterranean, especially those of the Valencian territory. The spores or seeds are collected from natural populations, trying to collect as much genetic diversity as possible.
All this work would be useless if they were not preserved: they are cleaned and dehydrated to 5% humidity. Then they are put in an airtight jar with silica gel, which absorbs moisture, and is stored in cold rooms between 18 and 24 degrees below zero. Under these conditions the viability of the seed is more than a century, it can even reach thousands of years. In this way, when the gardener who delivered it or the researcher who found it has died, and although no one has used them, they will not have been lost.
Web: www.comav.upv.es/comav_banco.html
Quantum information: the subatomic revolution
For more than 20 years, some scientists have been trying to take advantage of the rules that govern the quantum world to bring about a radical change in the fundamentals of computing. The callquantum computingIt is, today, in fashion, and in recent years this utopia seems to be much closer.
The fundamentals of quantum physics clash with traditional intuition and logic. It is not at all obvious to discover that the measurement of a physical quantity in a quantum system does not always produce the same result. However, despite this apparent uncertainty, the theory indicates with absolute precision what values can be obtained and with what probabilities they must appear. Of course, the surprise is just around the corner because it is difficult to assume that any measurement carried out affects the quantum system in such a way that it pushes it to a new state (it is as if weighing ourselves on a scale changes our weight). Furthermore, this final state depends on both the initial state of the system and the result of the measurement performed. Quantum theory turns out to our eyes – used to stones, cars and people – totally counterintuitive.
As we all know, information is stored on a computer in discrete pieces calledbits. Each bit can be equal to 0 or 1. In a digital computer a bit of information is represented by a certain electrical situation. For example, a charged capacitor can be 1, and a discharged one, 0. If we look closely, the bit is nothing more than a quantum of information. Can we create quantum systems that work like a capacitor? There are several types of devices that have been proposed to perform quantum computing. In a quantum computer, the basic information storage is carried out in a quantum system with two independent states: the qubit (quantum bit). The big difference between bit and qubit is that while classical bits are independent of each other, quantum qubits can interfere with each other, forming what physicists call collectively entangled states. This fact dramatically increases the speed with which some operations can be performed.
This is the field of research of the Spanish Ignacio Cirac, director of the theoretical division of the Max Planck Institute of Quantum Optics and visiting professor at the Institute of Photonic Sciences of Barcelona and one of the world’s leading experts in this line of research.
Web: www.icfo.es/index.php?section=people0&lang=english&op=show_card&people_id=29&nick=Ignacio%20Cirac
Autopia: driverless cars
In theInstitute of Industrial Automation of the CSICthey try to get robots that move and act by themselves. The simplest thing is to design the movement system: they can be legs (useful for rare terrain, such as climbing the sides of ships) although the usual thing is the wheels. More difficult to achieve is that they move without human assistance. This is where Ricardo García’s group focuses its efforts: cars controlled by a computer linked to a sensory system that recognizes the environment.
In Arganda del Rey they have built a fake neighborhood,ZOCO, ZOna of Conduction. In order for the car to move through this environment, GPS and an artificial vision system, developed at the University of Alcalá de Henares, is used, which recognizes the road and the obstacles located on it. To coordinate all this, it uses as a control system thefuzzy logic, which simulates the behavior of a human driver and allows you to control a car with instructions identical to those of normal language. Thus, the computer does not have to solve differential equations that explain their dynamics, but simply respond to instructions such as “if you are near a corner, brake” or “if you have moved a little to the left, move the steering wheel to the right. “. The car obeys and does things well … most of the time. What researchers want to achieve is that you always do what is asked of you.
It sounds like science fiction but in the next few years it is likely that we will see how some of these devices will be incorporated into our vehicles: in a traffic jam, so that we do not have to wait to move the car little by little, or take the car to a parking and parking alone. In fact, systems are already on the market that automatically move the car’s steering wheel to park, leaving the driver in control of the pedals.
Web: www.iai.csic.es/autopia/
Proteins on a computer
The most fascinating thing about biology is understanding how a cell works at the molecular level. Even more astonishing is that for the first time in history scientists think it can be solved, although it may take a century. It is clear that we are in an optimistic phase.
The famous “central dogma of molecular biology,” a gene codes for a protein, is long out of date. Nothing is as simple as it seems and each gene codes for many proteins. What’s more, there is 98% of our DNA that does not have this function and, although there are many hypotheses that try to explain what it is for, nothing is clear yet. The certain thing is that the size of the DNA does not correspond to the complexity of the organism: some plants have enormous genomes and they are not more complex. It may be that part of that DNA is historical remains and that it takes time for certain species to eliminate them; They can be repeated sequences, viruses that have been inserted …
Is life simple? We do not know, although we are now in a position to answer the question. Some experts think that if it were very complex it would be unstable. Of course, what they are clear about is that life is persistent. This indicates that there are robust mechanisms, which do not break easily; to be resistant, they must not contain many control mechanisms. Furthermore, the complexity of life does not seem to come from large control and regulation mechanisms, but from small details of the molecular interaction mechanisms. For example: the researcher thinks that a certain interaction of two proteins controls a process, so that they join in a certain place on the molecular surface. But, of course, they can also do it in a slightly different one with a little variation; they are simply two or three amino acids that have changed position together with a very small variation in energy. Knowing which of all these infinitesimal variants is correct is unpredictable with current technologies.
The great failure of molecular biology is its inability to predict how cells fold.protein. It is a physical problem, because at the bottom is what we really know about the interaction between atoms and water, about the entropy of water, about the interaction of water molecules … Our understanding of the underlying science It’s important: we can formulate the appropriate equations and do calculations. But the margin of error in our simulations is too great compared to what is actually available to determine the stability of proteins. That’s because they are built right on the edge: if they were just a little more unstable they would degrade and if they were more stable they wouldn’t do their job. It is this tightrope dance that makes the problem very complex. It is, in essence, a lack of physics.
This is one of the fields of action of thebioinformatics, a discipline that is driven by theNational Institute of Bioinformatics, created in 2003 and directed by Alfonso Valencia.
Web: www.inab.org/
A net for magnetism
MAGMANet.The following words are hidden under this acronym:Molecular Approach to Nanomagnets and Multifunctional Materials. It is a network of European research groups in the field of molecular magnets, which goes beyond traditional magnets; it means getting new magnetic materials at the nanometer scale. But MAGMANet is so much more than that. We are talking about a European Network of Excellence with 15 “nodes” (research centers) that bring together 150 researchers from 10 countries. The most striking thing is that Spain has three: Barcelona (CSIC), Valencia (University of Valencia) and Zaragoza (University of Zaragoza and CSIC). With this, it becomes the country with the largest number of nodes (followed by France and Great Britain with two).
Fernando Palacio is the visible figure of MAGMANet in Zaragoza and a world expert inmolecular magnets: participated in the characterization of the first molecular magnet in history and his group, from the Institute of Materials Sciences of Aragon, holds the world record in the characterization of the organic magnet at the highest temperature. This network has received 11 million euros from the European Union and with them they intend to achieve a triple objective, defined by the wordsIntegration, ResearchYExcellence. Under this umbrella it is intended to establish a European virtual research institute (European Institute of Molecular Magnets) -one of its kind-, integrate industrial groups (IBM, Philips or Bosch, to mention the most powerful that have already done so), train scientists and postdoctoral students, promote fundamental lines of research for the future development of magnet applications molecular. And, as a fundamental point, disseminate the science of its laboratories among the population.
Technology transfer is of vital importance. This fact shows that the powerful IBM thinks that molecular magnets are going to constitute a turning point in the field of electronics, computing, biomedicine … According to many experts, within a few years current systems will be totally obsolete.
Web: http://www.magmanet-eu.net/
What does a molecule like you do …?
If there is something essentially difficult in chemistry, it is to establish theoretical models capable of predicting thereactivity of molecules. It consists of finding out why the molecules transform into each other, what makes them transform in a certain way and not in another. If this is achieved, the reactivity of the molecules can be directed.
We must bear in mind something important: substances can react in many ways. In chemistry it is very common to find an active molecule, for example a drug, of which if we change in an almost imperceptible way its structure becomes a very powerful toxic. Making a mistake in the reaction not only implies that an impurity is being generated, but that a molecule can be created that has totally undesirable effects.
Curiously, this type of very casual, sporadic reactions, of which their mechanism is unknown, has been aware since the end of the 19th century. In the old chemistry books you can find a final chapter entitledReactions without a reaction mechanism. In other words, it was impossible for them to know why they were taking place. Later, chemists Woodward and Hoffman discovered the rules by which they were governed. The problem they faced was that the available models were relatively rudimentary due to the inherent complexity of the computational processes. It was in the 80s and 90s when it was possible, for the first time, to approach his study.
Only with the advent of highly computational computers have these reactions been used as true tools to efficiently synthesize complicated molecules. These problems can be solved by trial and error: We try different conditions and reagents until we find the solution. But this path is very costly in time and money. The other possibility is to study by computer how they react and how to choose the path to take. Later in the laboratory it is verified if it is correct or if it is necessary to clarify what was found. Then new parameters are introduced, the model is changed or another path is generated and so on until the necessary self-consistency between theory and experiment appears, until everything fits.
In Spain the number of groups that move in this field, the so-called Computational Chemistry, is rather scarce. One of these groups is that of Molecular Reactivity and Drug Design at the University of the Balearic Islands, whose interest is the chemical-physical study of chemical reactions with biological implications. A thorough understanding of these reactions is interesting, not only in the world of chemistry, but also for biology, pharmacology and biomedicine in general. His research includes the design of new molecules capable of dealing with the defense systems that many bacteria have managed to develop against antibiotics.
Web: www.uib.es/depart/dqu/dqf/introc.htm
