Células da pele são convertidas diretamente em células do coração

As células adultas da pele se transformaram diretamente em células cardíacas pulsantes, eliminando a etapa de produção das chamadas células-tronco induzidas.

Metamorfose celular

Cientistas do Instituto Scripps, nos Estados Unidos, converteram células adultas da pele humana diretamente em células funcionais do coração, de forma eficiente e sem ter que primeiro passar pelo complicado processo de gerar células-tronco embrionárias.

O mecanismo inédito poderá levar a novos tratamentos para uma variedade de doenças e lesões envolvendo a perda de células, tais como ataques cardíacos, Parkinson e Alzheimer.

"Este trabalho representa um novo paradigma na reprogramação de células-tronco," afirma o Dr. Sheng Ding, que conduziu o estudo. "Esperamos que isso ajude a superar os principais obstáculos de segurança e outros desafios técnicos atualmente associados com alguns tipos de terapias com células-tronco."

O trabalho será publicado no próximo exemplar da revista Nature Cell Biology.

Produzindo células-tronco

Conforme o corpo humano se desenvolve, as células-tronco embrionárias se multiplicam e se transformam em tipos mais maduros de células, através de um processo conhecido como diferenciação, gerando todos os diferentes tipos de células e tecidos do corpo.

Passada a fase embrionária, no entanto, o corpo humano tem uma capacidade limitada para gerar novas células para substituir as que foram perdidas ou danificadas.

Assim, os cientistas vêm tentando desenvolver formas de "reprogramar" as células humanas adultas de volta a um estado mais parecido com o embrionário, ou pluripotentes, de onde elas seriam capazes de se dividir e se transformar em qualquer um dos tipos de células do corpo.

Usando estas técnicas, os cientistas esperam um dia serem capazes de pegar as células de um paciente, como as células da pele, transformá-las em células do coração ou do cérebro, e inseri-las de volta no paciente para consertar tecidos danificados.

Dificuldades no uso das células-tronco

Em 2006, cientistas japoneses conseguiram reprogramar células da pele de um rato para que elas se tornassem pluripotentes, simplesmente inserindo um conjunto de quatro genes nas células - veja Células da pele são transformadas em células-tronco embrionárias.

Embora a tecnologia para gerar estas células, chamadas de células-tronco pluripotentes induzidas (iPS), represente um grande avanço, há alguns obstáculos a superar antes que elas possam ser adaptadas às terapias.

"Leva muito tempo para gerar células iPS e, em seguida diferenciá-las em células funcionais de tecidos específicos," diz Ding, "e é um processo tedioso. Além disso, o que você gera não é o ideal."

Leva de duas a quatro semanas para criar células iPS a partir de células da pele, e o processo está longe de ser eficiente, com apenas uma célula, dentre milhares, sendo capaz de fazer a transformação completa.

De posse das iPS, é necessário outro período de duas a quatro semanas para induzir essas células pluripotentes induzidas a se diferenciarem nos tipos de células desejadas.

E o processo de geração de células maduras a partir das células iPS não é infalível. Quando, por exemplo, os cientistas induzem as células iPS a se tornarem células cardíacas, as células resultantes são uma mistura de células do coração e algumas células iPS remanescentes.

Os cientistas sabem que injetar essas novas células cardíacas (juntamente com as células pluripotentes restantes) nos pacientes pode ser perigoso - quando as células pluripotentes são injetadas em camundongos, elas provocam o crescimento de tumores semelhantes ao câncer.

Devido a estas preocupações, Ding e seus colegas decidiram tentar ajustar o processo, eliminando completamente o estágio das iPS e indo diretamente de um tipo de célula madura (uma célula da pele) para outro (uma célula do coração).

De um tipo de célula diretamente a outro

A equipe introduziu em fibroblastos da pele de adultos os mesmos quatro genes inicialmente usados para fazer as células iPS.

Mas, em vez de deixar os genes continuamente ativos nas células durante várias semanas, eles os desligaram após alguns dias, muito antes de as células se transformarem em células iPS.

Ao desligar os quatro genes, os cientistas deram às células um sinal para fazê-las se transformar em células cardíacas.

"Em 11 dias, saímos de células da pele para células pulsantes do coração em um recipiente de vidro," disse Ding. "Foi fenomenal ver isto."

Ding ressalta que a técnica é fundamentalmente diferente do que tem sido feito por outros cientistas, e assinala que, dando às células um tipo diferente de sinal poderia transformá-las em células do cérebro ou células pancreáticas, por exemplo.

Além de compreender melhor a biologia básica das células-tronco, o próximo passo previsto pela equipe será modificar essa técnica para eliminar a necessidade de inserção dos quatro genes, que têm sido associados com o desenvolvimento de câncer quando as células são inseridas em um organismo vivo.

Romã pode se tornar fonte de ingredientes antioxidantes

Antocianinas da romã

Considerada desde o império romano como um símbolo de riqueza, a romã contém, entre os diversos compostos bioativos, as antocianinas.

Os cientistas brasileiros também vão estudar o óleo obtido por prensagem das sementes da romã.

Assim como a vitamina C, vitamina E e o betacaroteno, por terem deficiência de elétrons, as antocianinas captam facilmente os radicais livres.

Esses radicais, se produzidos ou absorvidos em excesso, aumentam os riscos para doenças como hipertensão, cataratas, artrite e envelhecimento precoce.

Isso pode ocorrer principalmente quando há demasiada ingestão de bebidas alcoólicas, estresse intenso e muita exposição à poluição, ao tabaco e ao Sol, situações que danificam as células saudáveis.

De acordo com estudos da Universidade de Baroda, na Índia, o fruto tem três vezes mais capacidade antioxidante do que o vinho e o chá verde. Não é por acaso que os povos árabes acreditavam em suas propriedades para fins medicinais.

Compostos da romã

Agora, a Embrapa, juntamente com a Universidade Federal do Rio de Janeiro (UFRJ), está tentando desenvolver novas técnicas para o aproveitamento desses elementos da fruta.

O mercado para a romã no Brasil tem crescido consistentemente, o que tem ampliado as áreas cultivadas com o fruto.

A pesquisadora Regina Isabel Nogueira, da Embrapa Agroindústria de Alimentos (Rio de Janeiro), espera obter a antocianina e outros compostos bioativos concentrando-os e estabilizando-os por microencapsulação por um processo chamado spray drier.

Nesse processo, pequenas gotas de material líquido são recobertas com um fino filme protetor.

Os materiais microencapsulados (material ativo ou núcleo) são envoltos num material formador de filme (material de parede ou agente encapsulante) onde cápsulas extremamente pequenas podem liberar o conteúdo de forma controlada e sob condições específicas.

Trata-se de uma tecnologia inovadora que tem sido empregada com êxito na indústria de cosméticos, farmacêutica e alimentícia.

Óleo de romã

Também será estudado o óleo obtido por prensagem das sementes da fruta com o objetivo de caracterizar o perfil dos ácidos graxos e as propriedades que possam interessar à indústria de alimentos.

A pesquisadora ainda prevê a opção de cristalizar a casca da romã, expondo-a em contato com a calda de açúcar para reduzir em até 50% o teor de água. Com isto, a fruta aumenta seu tempo de conservação e diminui seu peso e volume, gerando economia no custo de transporte, além de adocicar seu sabor levemente ácido.

Este processo, por ser muito simples, poderá despertar o interesse de produtores como uma forma de apresentar a fruta para consumo de forma semelhante à encontrada hoje por meio do gengibre cristalizado.

Boosting Body's Immune Response May Hold Key to HIV Cure

ScienceDaily (Feb. 3, 2011) — Australian scientists have successfully cleared a HIV-like infection from mice by boosting the function of cells vital to the immune response.

This graphic shows a typical immune response to overwhelming virus infection, with and without IL-7 treatment. The upper panels show an overwhelming viral infection. Active SOCS-3 dampens the immune response; decreased T cell numbers and impaired function leads to establishment of a chronic viral infection. The lower panels show an overwhelming viral infection with IL-7 treatment. IL-7 represses SOCS-3 and the immune response is reinvigorated. T cell numbers increase and function is enhanced, allowing the immune system to clear the virus.

A team led by Dr Marc Pellegrini from the Walter and Eliza Hall Institute showed that a cell signaling hormone called interleukin-7 (IL-7) reinvigorates the immune response to chronic viral infection, allowing the host to completely clear virus. Their findings were released in the February 3 edition of the journal Cell.

Dr Pellegrini, from the institute's Infection and Immunity division, said the finding could lead to a cure for chronic viral infections such as HIV, hepatitis B and C, and bacterial infections such as tuberculosis, which are significant economic and global health burdens.

Current approaches to curing chronic infections tend to focus on generating a long-lived immune response to a specific disease. Dr Pellegrini, working with colleagues Mr Simon Preston and Mr Jesse Toe, and collaborators Professors Pamela Ohashi and Tak Mak from the Ontario Cancer Institute, argues that long-lived immune responses to chronic diseases are not always effective, and has instead concentrated on how the immune response can be manipulated to better fight infection.

"Viruses such as HIV and hepatitis B and C overwhelm the immune system, leading to establishment of chronic infections that are lifelong and incurable," Dr Pellegrini said. "Despite tremendous efforts, long-lived immune responses for some of these viruses are ineffective, because the body is so overrun by virus that the immune system, in particular T cells, just give up trying to battle the infection. Some people have coined the phrase 'immune exhaustion' to explain the phenomenon. Our approach is to discover some of the mechanisms that cause this immune exhaustion, and manipulate host genes to see if we can boost the natural immune response in order to beat infection."

The team investigated the role of IL-7, a naturally-occurring immune hormone, in a mouse model of HIV infection. IL-7 is a cytokine (cell signalling hormone) that plays a critical role in immune system development and maintenance.

"We found that IL-7 boosted the immune response in a pretty profound fashion, such that animals were able to gradually clear the virus without too much collateral tissue damage," Dr Pellegrini said.

Further investigations revealed that, at the molecular level, IL-7 switched off a gene called SOCS-3.

"In an overwhelming infection, SOCS-3 becomes highly activated and suppresses the immune response, probably as a natural precaution to prevent 'out-of-control' responses that cause collateral damage to body tissue," Dr Pellegrini said. "In the case of these overwhelming infections, the immune system effectively slams on the brakes too early, and the infection persists."

Mr Preston, who worked on the SOCS-3 studies, said that switching off the SOCS-3 gene boosted the immune system and helped the animals to completely eliminate the infection.

"The key for us was figuring out that turning off SOCS-3 only really worked when it was within T cells," Mr Preston said. "It allowed the immune response to boost the number of virus-specific T cells and have an immune response good enough to eliminate the virus without initiating an immune response that was too large and would make the animal sick."

Dr Pellegrini said the research had provided excellent ideas for new therapies that could target and boost host immune cells to fight disease, rather than targeting the disease itself.

"The findings could help to develop drugs that target some of these host molecules, such as SOCS-3, and turn them off for very short, defined periods of time to reinvigorate the T cells, allowing them to regroup to fight infection," he said.

This research was supported by the Australian National Health and Medical Research Council, the Canadian Institute for Health and the Cancer Research Institute.

Mechanism Involved in Breast Cancer's Spread to Bone Discovered

ScienceDaily (Feb. 3, 2011) — In a discovery that may lead to a new treatment for breast cancer that has spread to the bone, a Princeton University research team has unraveled a mystery about how these tumors take root.

Breast cancer’s spread to the bone relies on interactions among tumor cells (blue); specialized bone cells that break down the bone, called osteoclasts (pink); specialized cells that rebuild bone tissue, called osteoblasts (brown); and the bone matrix. A “signaling protein" called Jagged1 sends destructive instructions that activate a group of molecules that work together, one molecule activating the next, in what’s called called the “Notch signaling pathway” (green flash) in the bone cells. Notch signaling stimulates the bone degrading activity of osteoclasts, releasing tumor growth factors such as the TGF-beta protein (red bubbles) from the bone matrix. Meanwhile, Notch signaling in bone-building osteoblasts increases the expression of another secreted protein, IL-6 (orange bubbles), which feeds back to tumor cells to promote their growth, forming a vicious cycle in bone metastasis.

Cancer cells often travel throughout the body and cause new tumors in individuals with advanced breast cancer -- a process called metastasis -- commonly resulting in malignant bone tumors. What the Princeton research has uncovered is the exact mechanism that lets the traveling tumor cells disrupt normal bone growth. By zeroing in on the molecules involved, and particularly a protein called "Jagged1" that sends destructive signals to cells, the research team has opened the door to drug therapies that could block this disruptive process. Doctors at other medical centers who have reviewed the research have found it promising.

"Right now we don't have many treatments to offer these patients," said Yibin Kang, an associate professor of molecular biology at Princeton who led the research team. "Doctors can manage the symptoms of this bone cancer, but they can't do much more. Our findings suggest there could be a new way of treatment," one that could slow or halt these bone tumors.

Breast cancer spreads to the bone in 70 to 80 percent of patients with advanced breast cancer, and it can also spread to the brain, lung and liver. Metastatic bone cancer is also a frequent occurrence among patients with advanced prostate, lung and skin cancers. In findings that will be published online in the journal Cancer Cell on Feb. 3, the team's research shows that breast tumor cells are able to give bone cells the wrong instructions through a process known as cell signaling -- with disastrous effects for the patient.

The billions of cells in a living human body must communicate to develop, repair tissue, and effectively maintain normal physiological functions. Cell signaling is part of a complex system that enables them to do that but, in patients with cancer, the relationship between signaling molecules and the molecules that communicate with them has gone awry.

Signaling molecules are those that can be received and read by a cell through a receptor molecule on its surface. Once the signaling molecules connect with a receptor, their union sets off a process that leads to the receiving cell changing its behavior. The sequence of events that follows involves a signaling pathway, which is a group of molecules that work together, one molecule activating the next until a specific function is carried out, such as renewing an organ's cells. There are many such signaling pathways.

But in the case of metastatic breast cancer, a disruptive pathway is formed. The signaling molecule, also known as a ligand, connects with a receptor molecule on certain bone cells and activates a cellular pathway that ultimately disrupts healthy bone renewal. Kang's team identified the signaling molecule as Jagged1, and the receptor molecule as one that activates a cellular pathway known as the "Notch pathway."

This finding gives cancer researchers a specific target, Kang said -- that of developing ways "to neutralize Jagged1's destructive power" and keeping it from interfering with normal bone growth.

At the Memorial Sloan-Kettering Cancer Center in New York City, Jacqueline Bromberg, a physician who also studies breast cancer, said the findings of Kang's team are promising.

"The bone is the most common site for metastasis in patients with breast cancer," said Bromberg, who met Kang several years ago while he was a postdoctoral fellow at Sloan Kettering. She noted that although there are treatments that can slow these tumors, such as estrogen-blockers, radiation and chemotherapy, "we have few therapies which effectively eradicate bone metastasis."

At the University of Indiana School of Medicine in Indianapolis, oncology professor Theresa Guise said the Princeton discoveries "show critical interactions between the tumor cells and bone cells." She added that the team has made a valuable contribution to research in that it "has dissected the contribution of the tumor and the micro-environment in this process."

Finding Has Link to Earlier Breast Cancer Work

The research builds on earlier work begun six years ago by Kang's laboratory that looked at how several different signaling pathways promote the spread of cancer to the bone. In a study published in the journal Nature Medicine in 2009, Kang showed that a pathway known as TGF beta plays a role in the growth of bone tumors. But until the recent study, it was not clear that Jagged1 plays a crucial role in that process. Before the current work focused on identifying the series of interconnected events that create the network of destructive pathways, Kang and Nilay Sethi, a dual degree student who recently finished his Ph.D. in molecular biology at Princeton, worked to find first which of the signaling molecules were at work in patients with breast cancer that had metastasized to the bone.

"It turned out that tumor samples from patients with breast cancer that had spread to the bone had higher levels of Jagged1," said Sethi, who is now completing his medical degree at the University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School.

The current research shows that, when the Jagged1 signaling molecule binds to its receptor molecule on the bone-producing cells, the interaction turns on the signaling pathway called Notch, and that leads to dramatic changes in bone growth. "It's like a key finding its matching lock, and opens a floodgate of information," Kang said. "Unfortunately, in this case, the Jagged1-Notch signaling is misused by cancer cells to serve a destructive purpose."

In healthy bone, specialized bone cells called osteoclasts scour the bone surface and use a combination of enzymes and acids to break down the old bone. Then another group of bone cells called osteoblasts deposit a new layer of bone matrix to rebuild the bone tissue. Working just like cellular excavators and paving machines, the bone-scrubbing osteoclasts and bone-building osteoblasts work in sync every day to renew the bone and maintain its strength. When these cells' activity gets out of balance, bone diseases can result.

While tumor cells lack the specialized tools that osteoclasts have to break down the bone, they are able to use the destructive Jagged1 molecule to disrupt the balanced activity of bone renewal, forcing the osteoclasts and osteoblasts to behave in a way that allows the tumor cells to invade the bone, Kang explained.

For example, by activating Notch signaling in osteoclasts, Jagged1 makes osteoclasts mature more quickly from their precursor cells, known as monocytes. A massive accumulation of these bone-scouring osteoclasts becomes the front line of the invasive force of tumor cells. That speeds up the breakdown of bone tissue and clears the way for tumor cells to expand into a malignant mass in the bone.

"Meanwhile, Jagged1 instructs the osteoblasts to secrete elevated levels of Interleukin-6, a tumor growth factor, so the cancer grows even faster," Kang said. "It's a one-two punch."

Creating further damage, the breakdown of the bone matrix releases a large quantity of another protein called TGF-beta, another signaling molecule that is embedded in the bone matrix during the bone-building process. In their earlier work published in 2009, Kang and colleagues showed that the TGF-beta protein derived from bones fuels the malignant growth of bone metastasis.

In the current study, some experiments conducted by Sethi established a surprising new link between TGF-beta and the Jagged1 molecule in bone metastasis.

"When tumor cells use the hijacked osteoclasts to break down the bone and release TGF-beta, it signals back to tumor cells to further stimulate the expression in Jagged1 in tumor cells," Sethi said. "The link between the Jagged1/Notch and TGF-beta pathways establishes a vicious cycle, essentially driving the unstoppable expansion of tumor and the destruction of skeletal tissues."

As a medical student, Sethi said he is acutely aware of the consequence of bone metastasis. "These patients suffer a lot. They have fractures, severe bone pain and debilitating nerve compression," he said. In addition, as the bone breaks down, calcium builds up in the blood, causing other life-threatening complications.

Blocking Destructive Pathway a Potential Treatment Path

The key to stopping the process appears to be finding a way to neutralize the Jagged1 signaling molecule or its receptor Notch.

Kang has several ideas on how scientists may learn how to do just that. One way to interrupt the destructive process is to put a roadblock in the Notch pathway. There is a way to do that by halting the activity of gamma secretase -- an enzyme that plays a key role when the Notch pathway is activated --because without it the delivery of instructions to bone cells cannot be completed. The pharmaceutical firm Merck & Co. has developed one such experimental drug that stops gamma secretase, known as a gamma secretase inhibitor or GSI, and the company has provided it to Kang's lab to support his team's work.

The drug has already shown promise treating metastatic bone cancer, Kang said. In animal experiments, the inhibitors have been proven to block the disease-causing signaling between tumor cells and bone cells, communication mediated by Jagged1 and Notch. Kang said GSI can reduce bone metastasis significantly, along with a dramatic reduction of bone destruction.

He hopes his team's new data showing that GSIs appear to work to halt the spread of cancer to the bone will result in clinicians starting a clinical trial of GSI to fight breast cancer metastases in the near future.

According to Kang, there are few drugs currently available to relieve symptoms associated with bone metastases, and none is able to completely stop the cancer. If Kang's findings lead to a drug that can halt or slow this process, it could affect the 200,000 patients that the NCI estimates are diagnosed every year with breast cancer. It might work for some other cancer patients as well, Kang said.

Sloan-Kettering's Bromberg said Kang's recent discovery "underlies the importance of targeting the environmental milieu" in which disease develops, in this case the activity of the Notch signaling pathway and specific interactions between cancer cells and the specialized cells that break down and rebuild bone.

Giant Virus, Tiny Protein Crystals Show X-Ray Laser's Power and Potential

ScienceDaily (Feb. 3, 2011) — Two studies published in the Feb. 3 issue of Nature demonstrate how the unique capabilities of the world's first hard X-ray free-electron laser -- the Linac Coherent Light Source, located at the Department of Energy's SLAC National Accelerator Laboratory -- could revolutionize the study of life.

The experimentally measured X-ray diffraction pattern of a single Mimivirus particle, imaged at the Linac Coherent Light Source, the world's first hard X-ray free-electron laser, located at SLAC National Accelerator Laboratory. Very short and extremely bright X-ray pulses can be used to obtain a single diffraction pattern from a large macromolecule, a virus or a cell before the sample explodes and turns into plasma. The structure of the virus can be determined from such patterns. In this study, the X-ray pulse lasted a millionth of a billionth of a second and heated the virus to 100,000 degrees Celsius, but not before this image was obtained. 

In one study, an international research team used the LCLS to demonstrate a shortcut for determining the 3-D structures of proteins. The laser's brilliant pulses of X-ray light pulled structural data from tiny protein nanocrystals, avoiding the need to use large protein crystals that can be difficult or impossible to prepare. This could lop years off the structural analysis of some proteins and allow scientists to decipher tens of thousands of others that are out of reach today, including many involved in infectious disease.

In a separate paper, the same team reported making the first single-shot images of intact viruses, paving the way for snapshots and movies of molecules, viruses and live microbes in action.

Led by Henry Chapman of the Center for Free-Electron Laser Science at the German national laboratory DESY and Janos Hajdu of Sweden's Uppsala University, the team of more than 80 researchers from 21 institutions performed these experiments in December 2009, just two months after the LCLS opened for research. Their studies are the first to demonstrate the power and potential of the LCLS for biology.

"The LCLS beam is a billion times brighter than previous X-ray sources, and so intense it can cut through steel," Chapman said. "Yet these incredible X-ray bursts are used with surgical, microscopic precision and exquisite control, and this is opening whole new realms of scientific possibilities," including the ability to observe atoms moving and chemical bonds forming and breaking in real time.

Outrunning a laser blast

In the experiments, scientists sprayed viruses or nanocrystals into the path of the X-ray beam and zapped them with bursts of laser light. Each strobe-like laser pulse is so brief -- a few millionths of a billionth of a second long -- that it gathers all the information needed to make an image before the sample explodes.

Hajdu had proposed this method nearly a decade earlier. Researchers at Arizona State University, Lawrence Livermore National Laboratory, SLAC and Uppsala spent years developing specialized equipment for injecting samples into the beam, and Germany's Max Planck Advanced Study Group brought in a 10-ton, $7 million instrument called CAMP to record every single photon of data with a fast, ultra-sensitive X-ray camera for later analysis.

Tests at DESY and Lawrence Berkeley National Laboratory showed that the concept worked at lower X-ray energies. "But as you go to higher energies, can you still outrun the damage?" said team member Michael Bogan, a SLAC staff scientist and principal investigator at the PULSE Institute for Ultrafast Energy Science, jointly located at SLAC and Stanford University. The answer, he said, was yes: "The physics still holds."

A big payoff from tiny crystals

The protein structure experiments were led by Chapman and Arizona State's John Spence and Petra Fromme. They chose as their target Photosystem I, a biological factory in plant cells that converts sunlight to energy during photosynthesis. It's one of an important class of proteins known as membrane proteins that biologists and drug developers are eager to understand better.

Embedded in cell membranes, these proteins control traffic in and out of the cell and serve as docking points for infectious agents and disease-fighting drugs; in fact, they are the targets of more than 60 percent of the drugs on the market. Yet scientists know the structures of only six of the estimated 30,000 membrane proteins in the human body, given the difficulty of turning them into big crystals for conventional X-ray analysis.

To get around this bottleneck, the researchers squirted millions of nanocrystals containing copies of Photosystem I across the X-ray beam. Laser pulses hit the crystals at various angles and scattered into the detector, forming the patterns needed to reconstitute images. Each crystal immediately vaporized, but by the time the next pulse arrived another crystal had moved into the bull's eye.

The team combined 10,000 of the three million snapshots they took to come up with a good match for the known molecular structure of Photosystem I.

"I attended several meetings this summer where this work was presented and I was extraordinarily excited by it," Michael Wiener of the University of Virginia, who was not involved in the research, said of the results. He leads one of nine institutes set up by the National Institutes of Health to decipher the structures of membrane proteins. "Preparation of these nanocrystals is likely to be very, very much easier than the larger crystals used to date," Wiener said, leaving scientists more time and money to find out how these important biomolecules work.

The team is scheduled to return to the LCLS this month to repeat the experiments with X-ray laser pulses that are much faster and deliver four times as much energy as they did in the initial round. If the physics still hold, future images should capture the extraordinarily complex structure of Photosystem I in atom-by-atom detail.

Portraits of a virus

For the second experiment, the team went a step beyond nanocrystals to no crystals at all. Led by Hajdu, they made single-shot portraits of individual virus particles. These snapshots are a step toward eventually producing stop-action movies of chemical changes taking place in molecules and within living cells.

Biologists have long dreamed of making images of viruses, whole microbes and living cells without freezing, slicing or otherwise disturbing them. This is one of the goals of the LCLS, and the researchers tested its capabilities on Mimivirus, the world's largest known virus, which infects amoebas.

Of the hundreds of Mimiviruses hit by the LCLS beam, two produced enough data to allow scientists to reconstitute their images. The images show the 20-sided structure of the Mimi's outer coat and an area of denser material inside, which may represent its genetic material. Shorter, brighter pulses focused to a smaller area should greatly improve the resolution of these images to reveal details as small as one nanometer, the team wrote in their Feb. 3 Nature report.

Getting a detailed picture of the internal structure of an individual virus "would be a great achievement," said team member Jean-Michel Claverie, director of the Structural & Genomic Information Lab in Marseille and one of the scientists who discovered Mimi's viral nature.

"This is a brand-new way to look at a biological object," he said. "This will allow us to address not only the questions related to the internal structure of the virus, but its intrinsic variability from one individual virus particle to the next -- a microscopic variability that might play a fundamental role in evolution."

The team returned to the LCLS in January to look at the Mimivirus at X-ray wavelengths that should maximize the amount of contrast and detail in the images. They will be analyzing the results in the months to come.

SLAC Director Persis Drell, who sat in a control room packed with scientists as raw data from the two experiments came in, said the experience was thrilling -- and so is the potential for biology and medicine.

"This first data and these first papers are really just the first view of a new research frontier," she said. "They represent a turning point for the LCLS, demonstrating new technologies that will be great steps forward."