Daily Archives: January 12, 2017

How photosynthetic pigments harvest light

Plants and other photosynthetic organisms use a wide variety of pigments to absorb different wavelengths of light. MIT researchers have now developed a theoretical model to predict the spectrum of light absorbed by aggregates of these pigments, based on their structure.

The new model could help guide scientists in designing new types of solar cells made of organic materials that efficiently capture light and funnel the light-induced excitation, according to the researchers.

“Understanding the sensitive interplay between the self-assembled pigment superstructure and its electronic, optical, and transport properties is highly desirable for the synthesis of new materials and the design and operation of organic-based devices,” says Aurelia Chenu, an MIT postdoc and the lead author of the study, which appeared in Physical Review Letters.

This photosynthetic antenna consists of several pigments, which collect light energy, and their associated proteins. Image courtesy of the researchers (edited by MIT News)

Photosynthesis, performed by all plants and algae, as well as some types of bacteria, allows organisms to harness energy from sunlight to build sugars and starches. Key to this process is the capture of single photons of light by photosynthetic pigments, and the subsequent transfer of the excitation to the reaction centers, the starting point of chemical conversion. Chlorophyll, which absorbs blue and red light, is the best-known example, but there are many more, such as carotenoids, which absorb blue and green light, as well as others specialized to capture the scarce light available deep in the ocean.

These pigments serve as building blocks that can be arranged in different ways to create structures known as light-harvesting complexes, or antennae, which absorb different wavelengths of light depending on the composition of the pigments and how they are assembled.

“Nature has mastered this art, evolving from a very limited number of building blocks an impressive diversity of photosynthetic light-harvesting complexes, which are highly versatile and efficient,” says Chenu, who is also a fellow of the Swiss National Science Foundation.

These antennae are embedded in or attached to membranes within cell structures called chloroplasts. When a pigment captures a photon of light, one of its electrons becomes excited to a higher energy level, and that excitation is passed to nearby pigments along a network that eventually leads to the reaction center. From that center, the available charge travels further through the photosynthetic machinery to eventually drive the transformation of carbon dioxide into sugar through a cycle of chemical reactions.

Chenu and Jianshu Cao, an MIT professor of chemistry and the paper’s senior author, wanted to explore how the organization of different pigments determines the optical and electrical properties of each antenna. This is not a straightforward process because each pigment is surrounded by proteins that fine-tune the wavelength of the photon emitted. These proteins also influence the transfer of excitation and cause some of the energy to dissipate as it flows from one pigment to the next.

Chenu and Cao’s new model uses experimental measurements of the spectrum of light absorbed by different pigment molecules and their surrounding proteins. Using this information as input, the model can predict the spectrum of light absorbed by any aggregation, depending on the types of pigments it comprises. The model can also predict the rate of energy transfer between each aggregate.

This technique has a long history in physics, and theorists have previously applied it to studying disordered solids, dipolar liquids, and other systems.

“This paper represents a novel extension of this technique to treat dynamic fluctuations arising from the coupling between pigments and protein environments,” Cao says.

The model provides, for the first time, a systematic link between the structure of antennae and their optical and electrical properties. Scientists working on designing materials that absorb light, using quantum dots or other types of light-sensitive materials, could use this model to help predict what kinds of light will be absorbed and how energy will flow through the materials, according to the antenna structure, Chenu says.

“The very long-term goal would be to have design principles for artificial light harvesting,” she says. “If we understand the natural process, then we can infer what is the ideal underlying structure, such as the coupling between pigments.”

Source: MIT, written by Anne Trafton

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Researchers use stem cells to regenerate the external layer of a human heart

A process using human stem cells can generate the cells that cover the external surface of a human heart — epicardium cells — according to a multidisciplinary team of researchers.

“In 2012, we discovered that if we treated human stem cells with chemicals that sequentially activate and inhibit Wnt signaling pathway, they become myocardium muscle cells,” said Xiaojun Lance Lian, assistant professor of biomedical engineering and biology, who is leading the study at Penn State. Myocardium, the middle of the heart’s three layers, is the thick, muscular part that contracts to drive blood through the body.

The Wnt signaling pathway is a group of signal transduction pathways made of proteins that pass signals into a cell using cell-surface receptors.

Heart progenitors cells derived from human stem cells can be further specified to become either heart cells belonging to the external layer, the epicardium, or the muscle layer, myocardium, of a human heart. Image credit: Lance Lian/Penn State

“We needed to provide the cardiac progenitor cells with additional information in order for them to generate into epicardium cells, but prior to this study, we didn’t know what that information was,” said Lian. “Now, we know that if we activate the cells’ Wnt signaling pathway again, we can re-drive these cardiac progenitor cells to become epicardium cells, instead of myocardium cells.”

The group’s results, published in Nature Biomedical Engineering, bring them one step closer to regenerating an entire heart wall. Through morphological assessment and functional assay, the researchers found that the generated epicardium cells were similar to epicardium cells in living humans and those grown in the laboratory.

“The last piece is turning cardiac progenitor cells to endocardium cells (the heart’s inner layer), and we are making progress on that,” said Lian.

The group’s method of generating epicardium cells could be useful in clinical applications, for patients who suffer a heart attack. According to the Centers for Disease Control and Prevention, every 43 seconds, someone in the United States has a heart attack

“Heart attacks occur due to blockage of blood vessels,” said Lian. “This blockage stops nutrients and oxygen from reaching the heart muscle, and muscle cells die. These muscle cells cannot regenerate themselves, so there is permanent damage, which can cause additional problems. These epicardium cells could be transplanted to the patient and potentially repair the damaged region.”

During their study, the researchers engineered the human stem cells to become reporter cells, meaning these cells expressed a fluorescent protein only when they became epicardium cells.

“We treated the cells with different cell signaling molecules, and we found that when we treated them with Wnt signaling activators, they became fluorescent,” said Lian.

Another finding, he said, is that in addition to generating the epicardium cells, the researchers also can keep them proliferating in the lab after treating these cells with a cell-signaling pathway Transforming Growth Factor Beta (TGF) inhibitor.

“After 50 days, our cells did not show any signs of decreased proliferation. However, the proliferation of the control cells without the TGF Beta inhibitor started to plateau after the tenth day,” said Lian.

The team will continue working together to further their research on regenerating endocardium cells.

“We are making progress on that inner layer, which will allow us to regenerate an entire heart wall that can be used in tissue engineering for cardiac therapy,” said Lian.

Source: Penn State University

A Not-So-Fine Kettle of Fish

That spicy tuna roll you order at your favorite sushi restaurant may not be tuna at all. And the yellowtail? It could be something else entirely. In fact, according to a new study, as much as half of nine types of fish sold in Los Angeles-area sushi restaurants may be mislabeled, despite tougher laws and increased media scrutiny in recent years.

The marine scientists from UC Santa Barbara’s National Center for Ecological Analysis and Synthesis (NCEAS), UCLA, Loyola Marymount University and UC Santa Cruz used DNA markers to identify seafood mislabeling over a four-year period at 26 restaurants and three high-end grocery stores in the greater Los Angeles area. Their findings appear in the journal Conservation Biology.

“The results of this study raise new questions about the efficacy of efforts intended to stem seafood fraud,” said co-author Samantha Cheng, a postdoctoral fellow at NCEAS who conducted the research as part of her graduate studies at UCLA. “Time and again, we found one variety or even an entirely different species to be labeled as a different, more commonly known or popular fish.”

The researchers took a novel approach to examining seafood fraud, enlisting the help of nearly 300 undergraduate students at UCLA as part of a marine biology course. The team targeted popular fish used for sushi, including red snapper, yellowtail, halibut, mackerel, salmon and four varieties of tuna: albacore, yellowfin, bigeye and bluefin. Between 2012 and 2015, students ordered these fish at restaurants or purchased sushi-grade specimens from grocers and took samples back to the labs for DNA analysis.

The investigators found that all of the restaurants served at least one mislabeled fish and that all fish types were mislabeled at least once, with the exception of bluefin tuna. Surprisingly, all menu items sold as red snapper or halibut were in reality a different fish. Mislabeling was slightly lower at the high-end grocery stores (42 percent) than at sushi restaurants (47 percent).

The names of fish caught in foreign countries may be lost in translation or mislabeling may occur in the country of origin, so Cheng emphasizes the importance of consumer awareness. She encourages people to ask questions about where the fish comes from and what the specific species is.

According to Cheng, mislabeling can significantly impact public health. In 2007, pufferfish sold as monkfish led to hospitalization of consumers in three states. “Finding that nearly a third of the halibut sushi examined were in fact olive flounder, a species that has caused rampant outbreaks of parasitic infections in Japan, is very concerning,” she explained.

In the paper, the researchers’ recommendations for curbing possible seafood mislabeling — which include increasing enforcement as well as the monitoring capacity of seafood inspectors — call for international and federal policies that strengthen traceability in seafood products.

Some efforts have been undertaken. On Dec. 8, 2016, the federal government released new seafood labeling and fish trade requirements. And the Obama administration on Jan. 9, 2017, issued new rules aimed at preventing unverifiable seafood from entering the U.S. market. Under the Seafood Import Monitoring Program, importers will be required to report information and maintain records about the harvest and chain of custody of fish.

“These are important first steps,” Cheng said. “But much more needs to be done to increase advocacy, detection and enforcement to prevent seafood fraud. The public deserves to know what they are eating. Particularly as sustainable foods are becoming more mainstream, consumers need to know whether their choices are adding pressure to already overharvested fisheries.”

Source: UC Santa Barbara

The Promise and Peril of Emerging Reproductive Technologies

In vitro fertilization has transformed reproductive medicine and sparked a number of therapeutic and diagnostic breakthroughs.

Now a new, still experimental, technique known as in vitro gametogenesis (IVG) is poised to usher in the next era in reproductive and regenerative medicine. The approach—thus far successful only in mice—allows scientists to create embryos in a lab by reprogramming any type of adult cell to become a sperm or egg cell.

An experimental approach known as in vitro gametogenesis allows scientists to reprogram any adult cell into an egg cell or sperm cell and develop embryos in the lab. Image credit: Luk Cox/Getty Images

In a newly published commentary, a trio of scholars argue that while IVG carries a promise to unravel the fundamental mechanisms of devastating genetic forms of infertility and to pave the way to a range of new therapies, the technique also raises a number of vexing legal and ethical questions that society should address before IVG becomes ready for prime-time clinical use in human patients.

The article, published Jan. 11 in Science Translational Medicine, is authored by I. Glenn Cohen, professor at Harvard Law School, George Q. Daley, dean of Harvard Medical School, and Eli Y. Adashi, professor of medical science and former dean of medicine and biological sciences at Brown University.

IVG holds enormous potential not only as a treatment for infertility, but also for a constellation of currently untreatable diseases, the authors write. Additionally, they note, the technique may provide an inexhaustible supply of lab-made embryonic stem cells for research and therapeutic use as a tantalizing alternative to scarce human embryonic stem cells, which are currently in limited supply due to ethical considerations and regulatory restrictions.

Yet, the authors say, such promises come with some worrisome scientific, legal and ethical challenges, such as the need for rigorous scientific protocols to ensure that any reproductive cells created through IVG are free of genetic aberrations, the threat of improper commercialization of IVG for large-scale embryonic generation and the use of preimplantation genetic screening to create “designer” offspring.

The authors acknowledge that clinical uses of IVG in the foreseeable future remain improbable at best. The impact of IVG, they say, will likely be limited to enhancing the science of germ cell biology. Yet, they caution, some clinical uses may arrive much sooner than anticipated, given the breakneck speed at which science and medicine are advancing.

To prepare for that time, scientists, bioethicists, policymakers, legal scholars and the public should initiate and maintain a vigorous conversation about the implications of IVG.

“Emerging technologies carry enormous promise but can also be profoundly disruptive. Aligning their promise with ethical and legal considerations is an imperative not only for scientists but for the society as a whole,” said George Q. Daley, dean of Harvard Medical School. “To do so, we must initiate vital conversations early and engage the public. Nothing less will do on our quest to ensure that we strike the right balance between our most audacious scientific pursuits and our core ethical and legal principles.”

The authors go on to say that the United States might be wise to borrow a page from the U.K.’s playbook, where a protocol focused on safety, ethics and public consultation has recently led to the launch of government-sponsored clinical studies of mitochondrial replacement therapy, a lab-based procedure that replaces defective mitochondrial DNA in a woman’s egg cells with healthy DNA to avert passing the defects to her offspring.

“IVG has the potential to upend one of the most traditional elements of human culture—our understanding of what parenthood is and how it occurs,” says Cohen, who is also the faculty director of thePetrie-Flom Center for Health Law Policy, Biotechnology and Bioethics at Harvard. “It is critical for law and medical ethics to grapple with the far-ranging implications of this new technology.”

Scientific and therapeutic promise of IVG

·      IVG could help scientists unravel the cellular and molecular aberrations responsible for DNA defects that cause a range of inherited diseases.

·      The technology may be used as a fertility-salvaging strategy in prepubertal children who undergo cancer treatments that damage their immature reproductive organs and tissues.

·      Certain inherited forms of infertility may become treatable by implanting healthy, genetically edited reproductive cells.

·      The approach could prevent devastating mitochondrial diseases by creating egg cells, or oocytes, free of mitochondrial DNA defects.

·      IVG may offer a safer alternative to traditional IVF treatments that require ovarian stimulation with injectable hormones, a procedure that carries a small but serious risk of harm.

Ethical perils, scientific challenges and legal considerations

·      Current reprogramming technology used to coax adult cells into becoming multipurpose cells has advanced by leaps and bounds, but it may be far from foolproof, the authors argue. Therefore, perfecting existing techniques before any clinical use is critical to ensuring that both the original adult cells and the multipurpose cells they give rise to are free of genetic and epigenetic aberrations.

·      Refining the science of IVG will, at least initially, require the generation and possible destruction of lab-made human embryos derived from stem cells. Under current U.S. law, such scientific pursuits would not be eligible for federal funding.

·      IVG has the potential to rapidly and cheaply generate multiple embryos, which could reignite age-old concerns about “embryo farming” and commodification of human reproduction.  How should regulators deal with that reality? Is the current federal and state scrutiny of sperm and egg banks an appropriate model?

·      Widespread clinical use of IVG may also spark worries about human enhancement via preimplantation genetic diagnoses. The practice is already used with traditional in vitro fertilization to screen embryos for serious genetic defects. However, with a potentially unlimited supply of IVG-generated embryos, there may be concerns that some parents could select embryos for offspring based on preferred genetic traits unrelated to disease and health.

·      Another potential concern is the prospect that IVG could enable direct gene modification via gene editing, which is now more feasible with emerging technologies like CRISPR. Hence, gene editing of germ cells could be practiced for genetic enhancement, raising considerable ethical concerns.

·      IVG also increases the risk for unauthorized—or even surreptitious—use of biological material such as hair or skin cells to generate human embryos. That possibility is not only ethically troubling but also raises worrisome legal questions cutting to the very core of the legal definition of parenthood.

Source: HMS

Tailored organoid may help unravel immune response mystery

What if you could design an adaptable, biomaterials-based model of an organ to track its immune response to any number of maladies, including cancer, transplant rejection and the Zika virus?

The lab of Ankur Singh, assistant professor in the Sibley School of Mechanical and Aerospace Engineering, has asked – and begun to answer – that very question.

Singh and a team of researchers from the Meinig School of Biomedical Engineering and Weill Cornell Medicine have developed a modular immune organoid that can replicate the anatomical structures found within lymph nodes. The organoid mimics the early stages of a germinal center, where B cell differentiation and initiation of immunological responses take place during infection.

By manipulating the components of the organoid, the researchers are able to dictate the action of the immune-cell response and demonstrate, for the first time in a controlled manner, the role of the lymph node’s environment in immune cell activation. And as opposed to two-dimensional models, the 3-D organoid enables much quicker and more plentiful replication of B cells, which are antibody-producing lymphocytes.

“This method presents the first lab-made 3-D immune tissue that allows you to change things found in immune organs once you get infected – the altered extracellular matrix, cell-cell interactions – and control the pace at which immune cell respond,” Singh said.

Their paper, “Modular immune organoids with integrin ligand specificity differentially regulate ex vivo B cell activation,” was published Dec. 13 in the American Chemical Society journal Biomaterials Science Engineering.

Co-lead authors were doctoral students Alberto Purwada and Shivem B. Shah of the Meinig School. Also contributing were Dr. Ari Melnick, the Gebroe Family Professor of Hematology/Oncology at Weill Cornell Medicine, and Wendy Beguelin, an instructor in the Melnick Lab.

A related paper, “Immuno-engineered organoids for regulating the kinetics of B-cell development and antibody production,” was published Dec. 22 in Nature Protocols, a journal geared to bench researchers. Singh and Purwada authored that work.

Germinal centers (GCs) are dynamic structures within lymphoid tissues that develop once B cells receive activation signals from surrounding immune cells in the presence of infection. During the GC process, naïve B cells (unexposed to antigens) differentiate into a specific immune marker (GL7) and then rearrange into high-affinity B cell receptors, but the underlying mechanisms of this progression aren’t understood.

Gaining a full understanding of those mechanisms, through the use of a “plug-and-play” system like the organoid that can be tailored to a specific disease, could provide better understanding of B cell biology and responses to a wide range of maladies, including cancer, asthma, arthritis and transplant rejection, along with faster responses to emerging infections such as H1N1 and Zika.

“Up to now, we have not been able to study the earliest steps of malignant transformation of cells in the immune system,” said Melnick, who is also a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine. “Now we can design experiments that will give us unprecedented understanding of how these tumors form, which will in turn provide critical insights into how to treat these diseases.”

Singh says the organoid – in either a synthetic polyethylene glycol or semi-synthetic gelatin-based platform – offers a quick and robust method for mimicking the GC microenvironment. That eliminates the need to implant the model inside a living creature.

“It’s living tissue that allows you to model certain parameters that you cannot do in vivo,” said Singh, who last week was selected to receive the top young investigator award from the Society for Biomaterials.

Singh said his group published its findings in Nature Protocols because they want the greater scientific community to know about it.

“Our goal was to make this technology available to scientists who can use this to understand immunology in a much better way,” he said. “I have a role and responsibility in advancing the science by putting this forward.”

More work in this area is ongoing, said Singh, who earlier this year was one of five Cornell recipients of a National Science Foundation CAREER award, which helped support this work. But he noted that the ability to drive immune reactions through the use of organoids will “grant us the ability to reproduce immunological events … for more rapid development and better understanding of B cells.”

This work was also supported by the National Institutes of Health.

Source: NSF, Cornell University