Scientists coax stem cells to form 3-D mini lungs

University of Michigan Health System

Scientists have coaxed stem cells to grow the first three-dimensional mini lungs. Previous research has focused on deriving lung tissue from flat cell systems or growing cells onto scaffolds made from donated organs.

In a study published in the online journal eLife the multi-institution team defined the system for generating the self-organizing human lung organoids, 3D structures that mimic the structure and complexity of human lungs.

Figure 1. Generation of three-dimensional ventral anterior foregut spheroids from endoderm monolayers.

(A) hESCs were differentiated into foregut endoderm by treating cells with 4 days of Activin A (ACTA) followed by 4 days of NOG+SB. (B) Foregut endoderm (NOG+SB) had high expression of the foregut marker SOX2 while the hindgut marker CDX2 was significantly reduced compared to untreated endoderm controls (End). NOG+SB monolayers had high expression of ventral anterior foregut genes NKX2.1 and PAX8 while the posterior foregut marker PDX1 was reduced. The foregut marker HHEX is expressed in the developing liver, biliary system, and thyroid and remained unchanged. (C) The majority of cells in NOG+SB treated cultures were SOX2 positive (green) compared to the control, in which only scattered clusters of cells were SOX2 positive. The scale bar represents 200 µm. (D) hESCs were differentiated into foregut spheroids by treating cells with 4 days of ACTA and then additional 4–6 days of NOG+SB+FGF4+Ch. Representative images of a spheroid in a matrigel droplet are shown as a whole mount image. Scale bar represents 100 µm. (E) Foregut spheroids (NOG+SB+FGF4+Ch) had high expression of the foregut marker SOX2 while the hindgut marker CDX2 was significantly reduced compared to untreated endoderm control (End) (top panel). Spheroids had high expression of anterior foregut genes NKX2.1 and PAX8 while the posterior foregut marker PDX1 was reduced and HHEX was unchanged (bottom panel). *p < 0.05, error bars represent SEM. (F) The majority of cells in foregut spheroids are FOXA2+ (green, left panel) and SOX2+ (white, right panel) and ECAD+ (red, right panel). Scale bar represent 50 µm.

DOI: http://dx.doi.org/10.7554/eLife.05098.003

Opinion: Science Counterculture. On taking DIYbio to the next level

FLICKR, ADONOFRIO

Open-source software paved the way for a new, community-driven development model by providing a product that was free to use and modify. This in turn fostered a business culture that was driven by support-services. That open-source principles could also herald a new era in biology was demonstrated by the successful completion of the publicly funded Human Genome Project more than a decade ago. Today, that same open, community-driven mindset continues to drive much research in the life sciences.

Soon after the human genome sequence was published, biohackers and do-it-yourself biology (DIYbio) groups came onto the scene. Among the first to demonstrate the feasibility of garage biology was Meredith Patterson, who created glow-in-the-dark yogurt by transfecting green fluorescent protein DNA into Lactobacillus. Rob Carlson, who in 2005 was among the first to spot this new development and start his own garage lab, opined in The Scientist in 2011 that garage innovation would be as important for technological advancements in biology as it was in IT. Since then, some biohackers have organized themselves into low-cost, community-based labs providing both lab space and training. However, unleashing their true technological potential will call for greater networking between these groups and borrowing concepts from business incubator models and the open-source hardware movement.

DIYbio groups—such as BioCurious, CounterCulture Labs, Genspace, Bioartlab, and Biogarage—have sprung up in many cities across North America, Europe, Asia, and Oceania. While many have demonstrated that simple experiments like isolating DNA or creating recombinant microbes are easily replicated outside the traditional lab, more promising, low-cost, open-source tools are also being developed. These include Biocurious’s bioprinter, OpenFuge, and the Kickstarter-backed OpenPCR. Of these, the latter two are already available, and at a fraction of the cost of the cheapest commercial models.

To grow, the DIYbio community must have access to inexpensive lab equipment and consumables. A number of companies, which include Open Biotechnology, IORodeo, and Chai Biotechnologies, are offering open-source products ranging from mammalian cell lines, electrophoresis kits, and power packs to thermal cyclers for PCR. While this list is by no means exhaustive, partnering with these and other similar startups could satisfy DIYbio’s thirst for machines and reagents, and help create innovative technologies.

And then there are the open-source hardware companies, such as SparkFun, Adafruit Industries, and MakerBot, as well as initiatives like RepRap, which are well positioned to serve the DIYbio community. SparkFun and Adafruit manufacture hardware components for DIY projects, such as Arduino microcontroller boards, printed circuit boards, and other accessories. MakerBot produces the Replicator 2 series of 3-D printers and RepRap is a community-based initiative for building self-replicating 3-D printers. Writing in Science, Michigan Technological University’s Joshua Pearce noted that Arduino-controlled research equipment fabricated on 3-D printers could soon become a reality. Members of Joseph DeRisi’s lab at the University of California, San Francisco, have already taken the first steps by 3-D printing lab consumables and equipment such gel electrophoresis combs, gel trays, and rotors for bench-top centrifuges.

While the ability of DIYbio to drive technological innovation is fairly obvious, its ability to spur basic research innovation is less clear. For this to happen, equipment and operating costs must be brought down. Technological innovation may well fuel research advances in the long run, but for now, DIYbio groups could focus on community outreach programs and targeting high school and university participation. Community labs that are up and running could invite students to volunteer. They could expand community outreach online by posting videos or providing links to educational sites. Networking among DIYbio groups to develop shared goals and invest in shared equipment could be one way out of the resource crunch. Another would be to borrow from the business incubator model by asking for a small percentage of equity in exchange for assistance in developing a successful product and bringing it to market.

Countercultural movements are evidence of a society’s diversity and vitality. Many of the biggest advances in science have come from people outside or on the fringes of the science establishment. The emerging DIYbio community could become the incubator that nurtures the next generation’s technologies and public scientists. For this to happen, DIY biologists will need to band together to gain the critical mass necessary to support the open-source development of biological techniques, equipment, and experimental methods.

ORIGINAL: The Scientist
By Usha Nair
December 9, 2013 

Usha Nair is a research associate in the department of biology at the University of Saskatchewan, where her research focuses on the structure determination of proteins associated with bacterial virulence.

Shushing RNA

ORIGINAL: The Scientist
By Edyta Zielinska

August 1, 2013

The cell detains potentially harmful RNA messages in the spliceosome long enough to create interfering RNAs against the aberrant messages.

 

GENOME JUMPERS: When unrestrained, transposons replicate and insert them­selves randomly throughout the genome. COURTESY OF PHILLIP DUMESIC, UCSF (Adapted from Transposon by Lauren Solomon, Broad Institute)

The paper
P.A. Dumesic et al., “Stalled spliceosomes are a signal for RNAi-mediated genome defense,” Cell, 152:957-68, 2013.

The finding
Although small interfering RNAs (siRNAs) are largely explored today for their potential in gene therapy, the phenomenon was first described in plants, which employ siRNAs to disable foreign RNA from viral infections. Researchers have since learned that siRNAs also play a role in suppressing transposable elements, which replicate and reinsert throughout the genome, occasionally disrupting the function of essential genes. Now, Hiten Madhani of the University of California, San Francisco, and colleagues have implicated the spliceosome, a molecular complex that excises introns from pre-messenger RNAs (pre-mRNAs), in siRNA-mediated suppression.

The splice of life
Like any gene, transposable elements are transcribed into pre-mRNAs that must be processed by the spliceosome. Madhani’s team noticed, however, that transposable-element pre-mRNAs appeared to be associated with spliceosomes more frequently than other pre-mRNAs.

The scan
When the researchers searched for proteins associated with the spliceosome and with siRNAs, they discovered a novel complex they dubbed spliceosome-coupled and nuclear RNAi, or SCANR, that appeared to be involved in producing siRNAs. Madhani reasoned that the spliceosome was “being used to recognize self- from nonself-DNA,” such as transposable elements. Such transcripts would have been introduced later in a cell’s evolution, and may not be optimized for the cell’s splicing machinery, causing it to stall, thereby giving SCANR more time to produce siRNA against the offending message.

The model
The paper reveals “an unexpected and previously unappreciated way for the cell to score an RNA as ‘aberrant’ and therefore in need of silencing,” says Erik Sontheimer, a researcher at Northwestern University.

Physicists, biologists unite to expose how cancer spreads

ORIGINAL: Princeton
by Catherine Zandonella

April 26, 2013; 01:00 p.m.

Cancer cells that can break out of a tumor and invade other organs are more aggressive and nimble than nonmalignant cells, according to a new multi-institutional nationwide study. These cells exert greater force on their environment and can more easily maneuver small spaces.

The researchers report in the journal Scientific Reports that a systematic comparison of metastatic breast-cancer cells to healthy breast cells revealed dramatic differences between the two cell lines in their mechanics, migration, oxygen response, protein production and ability to stick to surfaces. The researchers discovered new insights into how cells make the transition from nonmalignant to metastatic, a process that is not well understood.

The resulting catalogue of differences could someday help researchers detect cancerous cells earlier and someday prevent or treat metastatic cancer, which is responsible for 90 percent of all cancer deaths, according to the study. It was conducted by a network of 12 federally funded Physical Sciences-Oncology Centers (PS-OC) sponsored by the National Cancer Institute. PS-OC is a collaboration of researchers in the physical and biological sciences seeking a better understanding of the physical and chemical forces that shape the emergence and behavior of cancer.

(Image by Guillaume Lambert)

A multi-institutional study including researchers from Princeton University's Physical Sciences-Oncology Center found that metastatic cancer cells are more aggressive and nimble than nonmalignant cells. The Princeton group used silicon-etched microchannels (above) to study the behavior and physical properties of cancer cells. In this device, metastatic cancer cells enter the narrow channels at one end and accelerate as they rapidly move down the channel. Such high motility is a hallmark of metastasis and also indicative of high glucose metabolism, another hallmark of cancer.

"By bringing together different types of experimental expertise to systematically compare metastatic and nonmetastatic cells, we have advanced our knowledge of how metastasis occurs," said Robert Austin, professor of physics and leader of the Princeton PS-OC, along with senior co-investigator Thea Tlsty of the University of California-San Francisco.

Researchers with the Princeton PS-OC, for instance, determined that metastatic cells, in spite of moving more slowly than nonmalignant cells, move farther and in a straighter line, Austin said. The investigators studied the cells' behavior in tiny cell-sized chambers and channels etched out of silicon and designed to mimic the natural environment of the body's interior.

"The mobility of these metastatic cells is an essential feature of their ability to break through the tough membrane [the extracellular matrix] that the body uses to wall off the tumor from the rest of the body," Austin said. "These cells are essentially jail-breakers."

The tiny silicon chambers were built using Princeton's expertise in microfabrication technology — typically used to create small technologies such as integrated circuits and solar cells — and are an example of the type of expertise that physicists and engineers can bring to cancer research, Austin said. For the current study, the Princeton team included physics graduate students David Liao and Guillaume Lambert, and postdoctoral researchers Liyu Liu and Saurabh Vyawahare. They worked closely with a research group led by James Sturm, Princeton's William and Edna Macaleer Professor of Engineering and Applied Science and director of the Princeton Institute for the Science and Technology of Materials (PRISM) where the microfabrication was done.

The Princeton PS-OC also includes collaborators at the Johns Hopkins University School of Medicine, the Salk Institute for Biological Studies and the University of California-Santa Cruz.

The nationwide PS-OC program aims to crack the difficulty of understanding and treating cancer by bringing in researchers from physics, engineering, computer science and chemistry, said Nastaran Zahir Kuhn, program manager for the PS-OC at the National Cancer Institute.

Other notable findings from the paper include that metastatic cells recover more rapidly from the stress of a low-oxygen environment than nonmetastatic cells, which is consistent with previous studies. Although the low-oxygen environment did kill many of the metastatic cells, the survivors rebounded vigorously, underscoring the likely role of individual cells in the spread of cancer. The study also looked at total protein production and detected proteins in the metastatic cells that are consistent with the physical properties such as mobility that malignant cells need to invade the extracellular matrix.

"The PS-OC program aims to bring physical sciences tools and perspectives into cancer research," Kuhn said. "The results of this study demonstrate the utility of such an approach, particularly when studies are conducted in a standardized manner from the beginning."

For the nationwide project, nearly 100 investigators from 20 institutions and laboratories conducted their experiments using the same two cell lines, reagents and protocols to assure that results could be compared. The experimental methods ranged from physical measurements of how the cells push on surrounding cells to measurements of gene and protein expression.

"Roughly 20 techniques were used to study the cell lines, enabling identification of a number of unique relationships between observations," Kuhn said.

For example, a technique known as atomic force microscopy indicated that metastatic cells are softer than nonmalignant cells whereas a different technique, traction force microscopy, suggested that metastatic cells exert more force on their surroundings, Kuhn said. Together these two findings may indicate that metastatic cells can exert force to stick to, migrate on and remodel the tough extracellular matrix that surrounds the tumor, while remaining flexible enough to squeeze through small spaces in that membrane.

Secrets of Human Speech Uncovered

ORIGINAL: UCSF

By Jason Bardi
February 20, 2013

Work at UCSF Shows Brain Exerts Symphony-Like Control of Vocal Tract During the Act of Speaking

A team of researchers at UC San Francisco has uncovered the neurological basis of speech motor control, the complex coordinated activity of tiny brain regions that controls our lips, jaw, tongue and larynx as we speak.

Edward Chang, MD

Described this week in the journal Nature, the work has potential implications for developing computer-brain interfaces for artificial speech communication and for the treatment of speech disorders. It also sheds light on an ability that is unique to humans among living creatures but poorly understood.

“Speaking is so fundamental to who we are as humans – nearly all of us learn to speak,” said senior author Edward Chang, MD, a neurosurgeon at the UCSF Epilepsy Center and a faculty member in the UCSF Center for Integrative Neuroscience. “But it’s probably the most complex motor activity we do.”

The complexity comes from the fact that spoken words require the coordinated efforts of numerous “articulators” in the vocal tract – the lips, tongue, jaw and larynx – but scientists have not understood how the movements of these distinct articulators are precisely coordinated in the brain.

To understand how speech articulation works, Chang and his colleagues recorded electrical activity directly from the brains of three people undergoing brain surgery at UCSF, and used this information to determine the spatial organization of the “speech sensorimotor cortex,” which controls the lips, tongue, jaw, larynx as a person speaks. This gave them a map of which parts of the brain control which parts of the vocal tract.

They then applied a sophisticated new method called “state-space” analysis to observe the complex spatial and temporal patterns of neural activity in the speech sensorimotor cortex that play out as someone speaks. This revealed a surprising sophistication in how the brain's speech sensorimotor cortex works.

They found that this cortical area has a hierarchical and cyclical structure that exerts a split-second, symphony-like control over the tongue, jaw, larynx and lips.

“These properties may reflect cortical strategies to greatly simplify the complex coordination of articulators in fluent speech,” said Kristofer Bouchard, PhD, a postdoctoral fellow in the Chang lab who was the first author on the paper.

In the same way that a symphony relies upon all the players to coordinate their plucks, beats or blows to make music, speaking demands well-timed action of several various brain regions within the speech sensorimotor cortex.

Brain Mapping in Epilepsy Surgery 

The patients involved in the study were all at UCSF undergoing surgery for severe, untreatable epilepsy. Brain surgery is a powerful way to halt epilepsy in its tracks, potentially completely stopping seizures overnight, and its success is directly related to the accuracy with which a medical team can map the brain, identifying the exact pieces of tissue responsible for an individual's seizures and removing them.

The UCSF Comprehensive Epilepsy Center is a leader in the use of advanced intracranial monitoring to map out elusive seizure-causing brain regions. The mapping is done by surgically implanting an electrode array under the skull on the brain’s outer surface or cortex and recording the brain’s activity in order to pinpoint the parts of the brain responsible for disabling seizures. In a second surgery a few weeks later, the electrodes are removed and the unhealthy brain tissue that causes the seizures is removed.

This setting also permits a rare opportunity to ask basic questions about how the human brain works, such as how it controls speaking. The neurological basis of speech motor control has remained unknown until now because scientists cannot study speech mechanisms in animals and because non-invasive imaging methods lack the ability to resolve the very rapid time course of articulator movements, which change in hundredths of seconds.

But surgical brain mapping can record neural activity directly and faster than other noninvasive methods, showing changes in electrical activity on the order of a few milliseconds.

Prior to this work, the majority of what scientists knew about this brain region was based on studies from the 1940’s, which used electrical stimulation of single spots on the brain, causing a twitch in muscles of the face or throat. This approach using focal stimulation, however, could never evoke a meaningful speech sound. 

Chang and colleagues used an entirely different approach to studying the brain activity during natural speaking brain using the implanted electrodes arrays. The patients read from a list of English syllables – like bah, dee, goo. The researchers recorded the electrical activity within their speech-motor cortex and showed how distinct brain patterning accounts for different vowels and consonants in our speech.

“Even though we used English, we found the key patterns observed were ones that linguists have observed in languages around the world – perhaps suggesting universal principles for speaking across all cultures,” said Chang.

The article, “Functional organization of human sensorimotor cortex for speech articulation” is authored by Kristofer E. Bouchard, Nima Mesgarani, Keith Johnson and Edward F. Chang. It appears in the February 20, 2012 issue of the journal Nature. After this date, the article can be accessed at: http://dx.doi.org/10.1038/nature11911

This work was funded by the National Institutes of Health via grant #R00-NS065120, #DP2-OD00862 and #R01-DC012379 and by the Ester A. and Joseph Klingenstein Foundation.

Jugando con sistemas biológicos

ORIGINAL: MIT News
Anne Trafton, MIT Oficina de Noticias
21 de febrero 2012

Ingeniero Biológico Chris Voigt. Photo: M. Scott Brauer

Al intercambiar genes microbianos, Chris Voigt, diseña las células con nuevas funciones.

Las bacterias no suelen tomar fotografías. Tampoco atacar a las células tumorales o producir productos químicos. Pero con la ayuda de ingeniero biológico Chris Voigt, que pueden hacer todo eso y más.

Voigt, quien se unió a la facultad del MIT en julio como profesor asociado de ingeniería biológica, le gusta jugar con las bacterias y otros microbios para conseguir que lleven a cabo multitud de tareas útiles para las cuales nunca fueron creados por la naturaleza - un enfoque conocido como biología sintética.

Por ejemplo, para desarrollar su "cámara bacteriana", Voigt y sus alumnos añaden un sensor detector de luz de un alga en la bacteria E. coli, junto con un gen que causa que la bacteria produzca un pigmento negro. Una lámina de estas bacterias actúa como la "película", y cuando una plantilla se coloca sobre la película y la luz brilla sobre ella, una imagen de las formas se imprime en la hoja de bacterias.

Del mismo modo, trabajando en tumores a la E. coli se le incorporan genes de otras bacterias que detectan niveles bajos de oxígeno y alta densidad celular, en la misma cantidad que en las condiciones que se encuentran frecuentemente en los tumores.

Voigt, había estado en la facultad de la Universidad de California en San Francisco antes de llegar al MIT, para continuar, vinculando genes con un circuito celular que desencadena la producción de una proteína llamada invasina que permite a E. coli invadir las células de mamíferos.

A pesar de todo Voigt ha logrado en la biología sintética, entró en el campo casi por accidente. Como estudiante en la Universidad de Michigan, se especializó en ingeniería química, centrándose principalmente en los estudios teóricos de la mecánica de reacción y catálisis. Pero un día, que él estaba en el edificio de Química para recoger un examen, y un profesor que lo vio de pie cerca de su puerta, le invitó a entrar, pensando que era un estudiante que había solicitado un trabajo de verano. (El alumno no se presentó.)

"Yo estaba parado allí, así que empezamos a hablar", recuerda Voigt. "Él estaba haciendo plegamiento de proteínas y por el trabajo que yo había estado haciendo sobre la catálisis, tuve la oportunidad de conversar con él sobre algunos de los fundamentos teóricos de plegamiento de proteínas, y así es como me dieron el trabajo. Así es como me metí en la biología, pero yo nunca había tenido realmente ni una de clase de ella."

En la escuela de posgrado en el Instituto de Tecnología de California, comenzó a trabajar en la evolución dirigida de proteínas - en concreto, el desarrollo de un programa de computadora que identificar los lugares en donde las mutaciones de una proteína producen una proteína mejor. Durante una temporada post-doctoral en la Universidad de California en Berkeley, se interesó en la biología sintética, que por entonces acababa de salir como un nuevo campo, basado en la idea de que los nuevos circuitos biológicos pueden ser ensambladas a partir de un conjunto de piezas estandarizadas - en este caso,  los genes.

En Berkeley, Voigt trabajó en la extracción de los circuitos genéticos de una bacteria llamada B. subtilis y la reconstitución en E. coli, por lo que podrían ser estudiadas de forma aislada. Al unirse a la facultad en la UCSF, que comenzó a trabajar en la construcción de circuitos simples, tales como un sensor que responda a un estímulo específico, lo que llevó a su cámara bacteriana.

Circuitos complejos

Voigt, que es co-director del MIT Center para Nueva Biología Sintética, ahora está trabajando en la construcción de sistemas mayores y más altamente interconectadas que incluyen sensores y circuitos que puedan responder a las entradas de los sensores.

"En este momento estamos integrando los componentes en una celda individual. Uno de los problemas con que está recibiendo todas las piezas que interactúan unos con otros ", dice. Otro reto es la prevención de las piezas que se supone que no interactúan lo hagan.

"Si usted quiere crear un sistema con 50 circuitos que están todos trabajando juntos como parte de un cálculo que la célula está ejecutando, entonces usted necesita que cada uno de esos circuitos individuales no interferir con los demás. Por lo tanto, se convierte en un problema difícil de construir de forma exponencial por cada nuevo circuito adicional y demostrar que no interactúa con todos los demás ", dice Voigt.

Tales circuitos complejos podrían constituir la base de los microbios que pueden regular sus propios procesos de fermentación - por ejemplo, la levadura que fermenta la biomasa en etanol, dice Voigt. La fermentación de etanol produce acetato, que es tóxico para la levadura, como un subproducto. Por lo tanto, la cubas de fermentación deben estar equipadas con sensores que detectan niveles peligrosos de acetato y tomar medidas correctivas, tales como frenar la entrega del suministro de alimentos de los microbios (glucosa).

Usando la biología sintética, es posible que este proceso de control podría ser transferido a las propias células. Células de levadura que sienten los niveles elevados de acetato y apagan sus propios transportadores de glucosa hasta que los niveles de acetato de volvan a bajar.

Voigt dice que él vino al MIT en parte debido a su enfoque en la ingeniería biológica como una manera de impactar una variedad de campos - no sólo la medicina sino también la agricultura, energía, química industrial, limpieza del medio ambiente y los materiales. Para ello, el nuevo Centro de Biología Sintética ha reclutado a investigadores de una amplia gama de fondos.

"Nuestra esperanza es que este lugar realmente reúne a diferentes personas con los mismos objetivos que pueden pensar innovadoramente acerca de los tipos de sistemas se pueden diseñar", dice Voigt.

Jugando con sistemas biológicos

ORIGINAL: MIT News
Anne Trafton, MIT Oficina de Noticias
21 de febrero 2012

Ingeniero Biológico Chris Voigt. Photo: M. Scott Brauer

Al intercambiar genes microbianos, Chris Voigt, diseña las células con nuevas funciones.

Las bacterias no suelen tomar fotografías. Tampoco atacar a las células tumorales o producir productos químicos. Pero con la ayuda de ingeniero biológico Chris Voigt, que pueden hacer todo eso y más.

Voigt, quien se unió a la facultad del MIT en julio como profesor asociado de ingeniería biológica, le gusta jugar con las bacterias y otros microbios para conseguir que lleven a cabo multitud de tareas útiles para las cuales nunca fueron creados por la naturaleza - un enfoque conocido como biología sintética.

Por ejemplo, para desarrollar su "cámara bacteriana", Voigt y sus alumnos añaden un sensor detector de luz de un alga en la bacteria E. coli, junto con un gen que causa que la bacteria produzca un pigmento negro. Una hoja de estas bacterias actúa como la "película", y cuando una plantilla se coloca sobre la película y la luz brilla sobre ella, una imagen de las formas se imprime en la hoja de bacterias.

Del mismo modo, trabajando en tumores a la E. coli se le incorporan genes de otras bacterias que detectan niveles bajos de oxígeno y alta densidad celular, en la misma cantidad que en las condiciones que se encuentran frecuentemente en los tumores. Voigt, había estado en la facultad de la Universidad de California en San Francisco antes de llegar al MIT, para continuar con, genes vinculados con un circuito celular que desencadena la producción de una proteína llamada invasina que permite a E. coli invadir las células de mamíferos.

A pesar de todo Voigt ha logrado en la biología sintética, se metió en el campo casi por accidente. Como estudiante en la Universidad de Michigan, se especializó en ingeniería química, centrándose principalmente en los estudios teóricos de la mecánica de reacción y catálisis. Pero un día, que él estaba en el edificio de Química para recoger un examen, y un profesor que lo vio de pie cerca de su puerta, le invitó a entrar, pensando que era un estudiante que había solicitado un trabajo de verano. (El alumno no se presentó.)

"Yo estaba parado allí, así que empezamos a hablar", recuerda Voigt. "Él estaba haciendo plegamiento de proteínas y por el trabajo que yo había estado haciendo sobre la catálisis, tuve la oportunidad de conversar con él sobre algunos de los fundamentos teóricos de plegamiento de proteínas, y así es como me dieron el trabajo. Así es como me metí en la biología, pero yo nunca había tenido realmente ni una de clases en ella. "

En la escuela de posgrado en el Instituto de Tecnología de California, comenzó a trabajar en la evolución dirigida de proteínas - en concreto, el desarrollo de un programa de computadora que identificar los lugares en donde las mutaciones de una proteína producen una proteína mejor. Durante una temporada post-doctoral en la Universidad de California en Berkeley, se interesó en la biología sintética, que por entonces acababa de salir como un nuevo campo, basado en la idea de que los nuevos circuitos biológicos pueden ser ensambladas a partir de un conjunto de piezas estandarizadas - en este caso,  los genes.

En Berkeley, Voigt trabajó en la extracción de los circuitos genéticos de una bacteria llamada B. subtilis y la reconstitución en E. coli, por lo que podrían ser estudiados de forma aislada. Al unirse a la facultad en la UCSF, que comenzó a trabajar en la construcción de circuitos simples, tales como un sensor que responda a un estímulo específico, lo que llevó a su cámara bacteriana.

Circuitos complejos

Voigt, que es co-director del MIT Center para Nueva Biología Sintética, ahora está trabajando en la construcción de sistemas mayores y más altamente interconectadas que incluyen sensores y circuitos que puedan responder a las entradas de los sensores.

"En este momento estamos integrando los componentes en una celda individual. Uno de los problemas con que está recibiendo todas las piezas que interactúan unos con otros ", dice. Otro reto es la prevención de las piezas que se supone que no interactúan lo hagan.

"Si usted quiere crear un sistema con 50 circuitos que están todos trabajando juntos como parte de un cálculo que la célula está ejecutando, entonces usted necesita cada uno de esos circuitos individuales para no interferir con los demás. Por lo tanto, se convierte en un problema difícil de construir de forma exponencial cada nuevo circuito adicional y demostrar que no interactúa con todos los demás ", dice Voigt.

Tales circuitos complejos podrían constituir la base de los microbios que pueden regular sus propios procesos de fermentación - por ejemplo, la levadura que fermenta la biomasa en etanol, dice Voigt. La fermentación de etanol produce acetato, que es tóxico para la levadura, como un subproducto. Por lo tanto, la cubas de fermentación deben estar equipadas con sensores que detectan niveles peligrosos de acetato y tomar medidas correctivas, tales como frenar la entrega del suministro de alimentos de los microbios (glucosa).

Usando la biología sintética, es posible que este proceso de control podría ser transferido a las propias células. Células de levadura que sienten los niveles elevados de acetato y apagan sus propios transportadores de glucosa hasta que los niveles de acetato de volver a bajar.

Voigt dice que él vino al MIT en parte debido a su enfoque en la ingeniería biológica como una manera de impactar una variedad de campos - no sólo la medicina sino también la agricultura, energía, química industrial, limpieza del medio ambiente y los materiales. Para ello, el nuevo Centro de Biología Sintética ha reclutado a investigadores de una amplia gama de fondos.

"Nuestra esperanza es que este lugar realmente reúne a diferentes personas con los mismos objetivos que pueden pensar innovadoramente acerca de los tipos de sistemas se pueden diseñar", dice Voigt.