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By Laurel Hamers

The evolutionary path from single-celled organisms to complex species with higher-order thought processes has been mapped out with some degree of certainty, but how the earliest life forms appeared has proven a more difficult question. What conditions prompted organic molecules to assemble into the building blocks of life?

At the recent Origin of Life Symposium in Lille Auditorium, hosted by the MBL Physiology course, a panel of four distinguished scientists shared their research and opinions on this complex topic.

“What makes this a really important question is not only that it’s fundamental to how we understand biology as a process of living systems, but it’s also really important to how we think about the fate of this planet,” said Jennifer Lippincott-Schwartz, Physiology course co-director and a principal investigator at the Eunice K. Shriver National Institute of Child Health and Human Development.

Center of the Milky Way Galaxy IV – Composite. Credit:  NASA/JPL-Caltech/ESA/CXC/STScI - NASA JPL Photojournal: PIA12348.

Center of the Milky Way Galaxy IV – Composite. Credit: NASA/JPL-Caltech/ESA/CXC/STScI – NASA JPL Photojournal: PIA12348.

The first speaker, MBL Distinguished Scientist Mitchell Sogin, gave a broad overview of historical and current theories on the origin of life, with an emphasis on the role of geological diversity. Different geological microenvironments could have generated the building blocks that eventually combined to create habitable environments, he said.

Jack Szostak, Professor of Genetics at Harvard Medical School and 2009 Nobel Laureate in Physiology or Medicine, took the stage next. He described the problem as a step-by-step process.

“We’re not worried so much about defining exactly where life began,” he said. “I think what’s important is to understand the pathway. There’s a whole series of processes from simple chemistry to more complicated chemistry, building up the building blocks of biology,” Szostak said. “The goal for the field for the moment is to understand one continuous pathway from chemistry to biology.”

Nilesh Vaidya, a postdoctoral fellow at Princeton University, discussed research on spontaneous RNA assembly that he had carried out as a graduate student at Portland State University. By demonstrating that small RNA fragments can form cooperative networks that evolve toward greater complexity, he argued that early RNA-like molecules might have used a similar tactic to support the emergence of early life.

Tony Hyman, managing director of the Max Planck Institute of Molecular Cell Biology and Genetics, offered a different perspective, focusing on how cytoplasmic organization may have fostered an environment conducive to the formation of early life. He argued that phase separation of organic molecules due to cytoplasmic organization would concentrate these molecules in certain spaces and facilitate reactions that might not occur at lower concentrations.

A group discussion at the end helped symposium attendees to integrate the topics that the four researchers had presented.

The purpose of the symposium was not to reach a conclusion about the origins of life—the speakers all admitted that this was a daunting, and likely impossible, task. Rather, by bringing together eminent researchers in the field, the symposium organizers hoped to foster discussion between scientists addressing the same question from different angles.

 

Adam Cohen instructing in the MBL Physiology course in 2014.
Credit: Tom Kleindinst

Adam Cohen, a faculty member and former student in the MBL’s Physiology course, is one of three winners of the inaugural Blavatnik Awards for Young Scientists. The awards, given by the Blavatnik Family Foundation and the New York Academy of Sciences, honor exceptional young U.S. scientists and engineers. Each laureate receives $250,000 – the largest unrestricted cash prize for early-career scientists. Cohen is Professor of Chemistry and Chemical Biology and Physics at Harvard University, and a Howard Hughes Medical Institute (HHMI) investigator.

Cohen was recognized for “significant breakthroughs in cellular imaging that allow for the observation of neural activity in real-time, at single-cell resolution.” Combining his expertise in chemistry, physics, and biology, Cohen uses microscopy and lasers to develop noninvasive methods of visualizing and studying the roles of cellular voltage in neurons. His novel techniques, including fluorescent voltage indicators derived from microbial rhodopsins, help to answer questions about the propagation of electrical signals and could one day lead to the design of individualized treatments for conditions such as ALS, epilepsy, and bipolar disorders.

“Cohen is recognized as one of the nation’s most promising young scientists,” said Vern Schramm, Ruth Merns Chair in Biochemistry at the Albert Einstein College of Medicine and a member of the 2014 Blavatnik Awards National Jury.

The two other 2014 Blavatnik National Laureates are Rachel Wilson, Professor of Neurobiology at Harvard University and an HHMI Investigator, who was recognized for her research on sensory processing and neural circuitry in the fruit fly; and Marin Soljačić, Professor of Physics at MIT, recognized for his discoveries of novel phenomena related to the interaction of light and matter, and his work on wireless power transfer technology.

The Blavatnik Family Foundation is headed by philanthropist Len Blavatnik, founder and chairman of Access Industries, a privately held U.S. industrial group.

By Laurel Hamers

One of the brain’s amazing abilities is self-repair: Although injury or illness may disrupt neural circuits, many connections will reform over time.

Artur Llobet, an MBL Research Awardee from the University of Barcelona, is spending his second consecutive summer in the Whitman Center for Visiting Research investigating olfactory neuron repair in Xenopus laevis, the African clawed frog.

Calcium labeling of olfactory sensory neurons' presynaptic terminals in a Xenopus laevis tadpole. Photo credit: Artur Llobet

Labelling of presynaptic terminals of olfactory sensory neurons in a Xenopus laevis tadpole using calcium green dextran. Image is pseudocolored so that yellow represents higher and blue lower calcium concentration.
Photo and caption: Artur Llobet

“One of the advantages of working with frogs is that they have fantastic regenerative capabilities,” says Llobet. Tadpoles are able to repair damaged neural circuits in a few days, making them ideal test subjects.

Llobet is working with a transgenic line of Xenopus tadpoles that express green fluorescent protein (GFP) in their neurons, allowing him to easily see the neural connections. Last year, he studied the timeframe of Xenopus neural repair by measuring how long snipped olfactory nerves took to regrow. Now, he is trying to understand in greater detail the mechanisms behind the repair process.

Neurons pass electrochemical messages between each other at junctions called synapses; when a neuron fires, the voltage change propagates along the nerve fiber (axon) and calcium increases at the presynaptic terminal, which releases neurotransmitters. By labeling the tadpoles’ synaptic terminals with calcium indicators, Llobet can visualize the functionality of the re-grown connections and determine when during the repair process the new synapses start signaling.

“In a GFP animal, we can see that the nerve has re-grown, but we don’t know if that nerve is actually working or not,” says Llobet. “So we look at the synapses and see whether the calcium concentration increases when we stimulate olfactory sensory neurons.” This calcium accumulation indicates that the new nerve is not just present, but also functional.

By examining neural repair in frogs, scientists hope to gain insight into this process in more complex systems such as the human brain.

Llobet’s research is taking place through the National Xenopus Resource (NXR) at the MBL, a center that maintains breeding stocks of frogs and provides training on advanced imaging and experimental technologies. According to Llobet, the specialized resources offered by the NXR make this research project possible. He is one of six MBL Research Awardees in 2014 to be using the animals and research services of the NXR, which is one of 28 National Institutes of Health-funded Animal Resource Centers nationwide and a cornerstone facility of the MBL’s Bell Center for Regenerative Biology and Tissue Engineering.

By Laurel Hamers

Our arms and legs normally work so fluidly that we may forget that their size and location were determined by complex genetic control during early development.

Keys to the precise regulatory ballet that makes our limbs look the way they do may be found in a seemingly dissimilar group of organisms: sharks and skates.

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Skates in the MBL’s Marine Resources Center. Photo credit: Laurel Hamers

Cartilaginous fish like sharks and skates are the oldest fish to have pectoral fins:  paired appendages that are the evolutionary predecessor of our arms. Tetsuya Nakamura, a postdoctoral researcher at the University of Chicago, is spending the summer at the MBL investigating these cartilaginous fish. He hopes to elucidate the molecular mechanisms responsible for the diversity of fin shapes in this single group of fish and, on a broader scale, the evolution of appendage shapes across species.

“The best way to understand the diversity of fin types is to study an extremely strange fish, like the skate,” says Nakamura. “The pectoral fins of skate are very wide—they’re totally different from other animals.”

Nakamura is focusing on Hox genes, which control body patterning during embryonic development; they are responsible, for example, for making sure your arms attach below your shoulders and not out the top of your head. Researchers can manipulate individual Hox genes and readily see structural differences in the body parts influenced by that gene.

By comparing expression patterns of Hox genes in the fins of skates and closely related sharks, Nakamura is identifying specific genes that may be responsible for the skate’s elongated pectoral fins compared to the shark’s narrower ones. He will then manipulate the expression of these genes in an attempt to alter fin shape.

The blue lines show the cartilage structure in the fins of two fish. Note the shark's narrow fins compared to the skate's wide, fan-like ones. Photo credit: Tetsuya Nakamura, composite image by Laurel Hamers

The blue lines show the cartilage structure in the fins of two fish. Note the shark’s narrow fins compared to the skate’s wide, fan-like ones. Photo credit: Tetsuya Nakamura, composite image by Laurel Hamers

“My opinion is that fin width is very important in deciding fin shape,” he says. “If I can control fin width, for example, to make narrower fin bases in skate, I think their fin shape would be like a shark’s.”

Nakamura, who is spending his first summer at MBL, is a member of Neil Shubin’s lab in the Department of Organismal Biology and Anatomy at UChicago.

A closeup of an Aedes aegypti mosquito biting its host. Photo credit: Alex Wild, alexanderwild.com

The yellow fever mosquito,  Aedes aegypti, biting its prey. Photo credit: Alex Wild, alexanderwild.com

By Laurel Hamers

It’s a question asked by many a summer stargazer: How do mosquitoes home in on their human prey, turning a relaxing evening into an itchy disaster?

Meg Younger, an MBL Grass Fellow and a postdoctoral scientist at Rockefeller University, is trying to find out by looking at mosquitoes’ neural responses to different combinations of odors.

Behavioral studies have identified several cues that are mildly attractive to mosquitoes: carbon dioxide, heat, and lactic acid, a component of sweat. Presented alone, none of these cues is particularly powerful; when paired together, however, their effects multiply.

“What we don’t know yet is how these stimuli that are ignored or only mildly attractive are transformed into very attractive stimuli in the brain when presented simultaneously,” Younger says.

Younger is using electrophysiology and calcium imaging to monitor olfactory neurons, looking for differences in brain activity when mosquitoes are presented with certain stimuli alone or in different combinations.

She is carrying out her research in the yellow fever mosquito, Aedes aegypti, which is found in tropical and subtropical areas and is the also the major vector for dengue fever and chikungunya.

“The more we know about how mosquitoes process different stimuli to find humans, the more potential we have to come up with creative ways to stop them from biting people and spreading diseases,” Younger says.

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