26 February 2015

MIT study details the degree to which urban movement is linked to social activity.


Courtesy of the researchers (edited by MIT News)

CAMBRIDGE, Mass. -- If you live in a city, you know that a fair amount of your movement around town is social in nature. But how much, exactly? A new study co-authored by MIT researchers uses a new method to infer that around one-fifth of urban movement is strictly social, a finding that holds up consistently in multiple cities.
The study used anonymized phone data that, unlike most data in the field, provides information that can be used to reconstruct both people’s locations and their social networks. By linking this information together, the researchers were able to build a picture indicating which networks were primarily social, as opposed to work-oriented, and then deduce how much city movement was due to social activity.
“Adding two data sources — one on the social side and one on the mobility side — and layering them one on top of each other gives you something that’s a little bit greater,” says Jameson Toole, a PhD student in MIT’s Engineering Systems Division, and one of the authors of a newly published paper outlining the study’s results.
“It’s a way to look at the data that wasn’t done before,” says Marta Gonzalez, an assistant professor in MIT’s Department of Civil and Environmental Engineering, and another co-author of the study.
By developing a new means of quantifying how much urban travel is based on social activity, the researchers believe they have started creating a new analytical tool that could be of use to planners and policymakers.
“There are a lot of people who need to have estimates of how people move around cities: transportation planners, and other urban planners,” Toole says. “But a lot of data-driven models don’t take into account social behavior. What we found is that … if you are trying to estimate movement in a city and you don’t include the social component, your estimates are going to be off by about 20 percent.”

Going mobile
The paper, “Coupling human mobility and social ties,” is appearing this week in Interface, a peer-reviewed journal published by the Royal Society. The co-authors are Toole, who is the lead author; Carlos Herrer-Yaque, of the Universidad Polytecnica in Madrid; Gonzalez, who is the principal investigator on the study; and Christian Schneider, an MIT post-doctoral researcher during the course of the study.
The study’s anonymized mobile phone data comes from three major cities in Europe and South America. By examining the locations of calls, the networks of calls made, and the times of contact, the researchers found that most people have essentially three kinds of social networks in cities: social companions (who they are around a lot in the evenings and on weekends), work colleagues (who they tend to contact during weekdays), and more distant acquaintances with whom people have more sporadic contact.
After distinguishing these networks from each other, the researchers were able to quantify the extent to which social activity was the primary cause of an urban trip; their conclusion falls within the bounds of previous, broader estimates, which have ascribed 15 to 30 percent of urban movement to social activity.
“It’s pretty rare you would find these patterns showing up by themselves in multiple cities,” Toole says. “It lends credence to the universality of this [pattern].”
In the paper, the researchers also build a model of urban social movement, which they call the “GeoSim” model; it extends previous models of urban mobility by adding a layer relating to social-activity choices. The model better fits the data in this study, and could be tested against future data sets as well.
“Big data is amazing,” Toole says, “but this adds the context back into the social networks and movements.”
The research was partly funded by the Accenture-MIT Alliance in Business Analytics, the Center for Complex Engineering Systems at MIT, and the National Science Foundation.

Written by Peter Dizikes, MIT News


Related links
Archive: Making sense of big data
http://newsoffice.mit.edu/2013/student-profile-jameson-toole-0326

ARCHIVE: Study: Commuting times stay constant even as distances change
http://newsoffice.mit.edu/2014/study-commuting-times-stay-constant-even-distances-change



Massachusetts Institute of Technology, 77 Massachusetts Avenue Building 11-400, Cambridge, MA 02139-4307 United States

25 February 2015

Stellate cells in the liver control regeneration and fibrosis

Caption: Liver fibrosis in a mouse: Labeling of
two characteristic proteins (yellow) shows
pathogenic changes in the organ.
Source: Carolin Mogler, DKFZ
Scientists from the German Cancer Research Center (DKFZ) and the Medical Faculty in Mannheim at Heidelberg University are searching for new approaches to prevent liver fibrosis. They have identified a surface molecule on special liver cells called stellate cells as a potential target for interfering with this process. When the researchers turned off the receptor, this led to reduced liver fibrosis and improved regeneration of hepatic cells.


Liver fibrosis, which is the progressive formation of scar tissue in the liver, is a massive medical problem. An estimated ten percent of the population is affected by liver fibrosis or its corresponding later stage, liver cirrhosis. A variety of causes can lead to liver fibrosis, the most widely recognized ones being alcohol consumption and virus-induced chronic liver inflammation. Other factors that can lead to scarring in the liver include the use of certain drugs, fatty liver disease and genetic disorders such as iron overload disease. As fibrosis progresses, the liver tissue becomes increasingly nodular, and the disease turns into liver cirrhosis, a dangerous condition that also drastically increases the risk of developing liver cancer.

The working group of Professor Hellmut Augustin at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) and the Medical Faculty in Mannheim at Heidelberg University has now detected a new molecule on the surface of hepatic stellate cells that is a major contributor to the development of liver fibrosis. Hepatic stellate cells are a type of specialized cell in the walls of blood vessels. Their functions in the liver include storing vitamin A and regulating blood flow. They are considered to be initiators of liver fibrosis: In the wake of liver damage, these cells produce key substances for the formation of scar tissue and release them into the surrounding environment. If the liver damage cannot be completely repaired by dividing liver cells, this scar tissue stays put, giving rise to liver fibrosis.

The scientists in Augustin's group have now discovered a protein called endosialin on the surface of hepatic stellate cells that activates these cells and, thus, also promotes the production of scar tissue. Genetically modified mice whose cells had no endosialin developed considerably less liver fibrosis after prolonged liver damage than normal animals whose cells were able to produce endosialin.

Surprisingly, the absence of endosialin not only reduced scarring and the activation of hepatic stellate cells but also improved the regenerative capacity of the remaining liver cells without leading to proliferative growth of the liver. Hence, endosialin can influence the critical balance between scar formation and liver regeneration.

Endosialin also appears to play a role in human liver fibrosis: The scientists examined samples from healthy liver tissue and from liver tissue at various stages of liver fibrosis, through to cirrhosis, to determine their levels of endosialin.

"Endosialin is produced at very elevated levels primarily in the early, active phase of liver fibrosis," explains Carolin Mogler, first author of the publication. "Many molecules are produced at different levels after liver damage, but we were very surprised by the extent to which the stellate cells increase the production of endosialin. These findings help us better understand how liver fibrosis develops."

These findings, obtained in a basic research setting, are still a long way from potential clinical application. However, an antibody that blocks endosialin is already being tested in clinical trials with the goal of treating specific types of tumors. The scientists now plan to investigate whether this antibody might also be useful for treating other diseases such as liver fibrosis.

Carolin Mogler, Matthias Wieland, Courtney König, Junhao Hu, Anja Runge, Claudia Korn, Eva Besemfelder, Katja Breitkopf-Heinlein, Dorde Komljenovic, Steven Dooley, Peter Schirmacher, Thomas Longerich, Hellmut G. Augustin: Hepatic stellate cell expressed Endosialin balances fibrogenesis and hepatocyte proliferation during liver damage.
EMBO Mol Med 2015, DOI: 10.15252/emmm.201404246



The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) with its more than 3,000 employees is the largest biomedical research institute in Germany. At DKFZ, more than 1,000 scientists investigate how cancer develops, identify cancer risk factors and endeavor to find new strategies to prevent people from getting cancer. They develop novel approaches to make tumor diagnosis more precise and treatment of cancer patients more successful. The staff of the Cancer Information Service (KID) offers information about the widespread disease of cancer for patients, their families, and the general public. Jointly with Heidelberg University Hospital, DKFZ has established the National Center for Tumor Diseases (NCT) Heidelberg, where promising approaches from cancer research are translated into the clinic. In the German Consortium for Translational Cancer Research (DKTK), one of six German Centers for Health Research, DKFZ maintains translational centers at seven university partnering sites. Combining excellent university hospitals with high-profile research at a Helmholtz Center is an important contribution to improving the chances of cancer patients. DKFZ is a member of the Helmholtz Association of National Research Centers, with ninety percent of its funding coming from the German Federal Ministry of Education and Research and the remaining ten percent from the State of Baden-Württemberg.

Contact:

Dr. Stefanie Seltmann
Head of Press and Public Relations
German Cancer Research Center
Im Neuenheimer Feld 280
D-69120 Heidelberg
T: +49 6221 42 2854
F: +49 6221 42 2968
presse@dkfz.de

Dr. Sibylle Kohlstädt
Press and Public Relations
German Cancer Research Center
Im Neuenheimer Feld 280
D-69120 Heidelberg
T: +49 6221 42 2843
F: +49 6221 42 2968
Email: presse@dkfz.de

20 February 2015

Food from the Sea

Research summit aims to inspire UC-wide collaborations around fisheries and aquaculture; inaugural event is part of UC Global Food Initiative

With a world population on track to hit 9 billion by 2050, the global demand for food is expected to explode apace. By some estimates, the demand for animal protein alone is projected to grow as much as 80 percent over that same 35-year period.
Ben Halpern is a professor at the Bren School, a center associate at UCSB's National Center for Ecological Analysis and Synthesis and lead scientist for the global Ocean Health Index.

Photo Credit: 

Sonia Fernandez

How will such ballooning needs be met? Is it even possible to do so without depleting ecosystems and decimating the environment?
A research conference held at UC Santa Barbara examined exactly that problem with an eye toward potential solutions — specifically those answers that may be found in the ocean.
“That’s a whopping amount of additional food to be produced, and the path that we take to meeting this demand really matters,” said Steven Gaines, dean of UCSB’s Bren School of Environmental Science & Management, during the first-ever Food from the Sea Summit. “Trying to produce that much food from land creates a big set of problems in terms of environmental impacts. 
“But,” Gaines added, “fixing fisheries, in most cases, lowers the environmental costs while increasing food production.”
How to fix overexploited fisheries and how to capitalize on the potential for aquaculture to play a key role in future food production — and how to do it all sustainably — were the central subjects on the table at the convening of scientists and experts from across the University of California and beyond.
Faculty from UC campuses including Davis, San Diego and Santa Cruz, in addition to Santa Barbara, gathered at the Food from the Sea Summit to share research past and present and, ideally, to spark new projects and inspire systemwide collaborations. The event was part of the UC Global Food Initiative, which is harnessing the UC’s collective excellence in research, outreach and operations in a sustained effort to develop, demonstrate and export solutions — throughout California, the U.S. and the world — for food security, health and sustainability.
The summit’s robust array of presentations covered, among other subjects, the seafood trade deficit and legal challenges for aquaculture production; ocean industrialization and ecosystem-based approaches to food security; the socio-ecological benefits and impacts of aquaculture; and predicting environmental tipping points to inform ecosystem management.
Ben Halpern, director of the Center for Marine Assessment and Planning, and a Bren School professor, presented recent results from the Ocean Health Index (of which he is lead scientist) that quantify the health of the ocean and the role of seafood in those assessments. He also offered a preview of a nascent effort that will use data from that index, and myriad other sources, to further illuminate the role of seafood in human health beyond the common focus on protein needs.
“We want to try to understand how changes in the marine environment impact abundance of seafood, which impacts catch, which impacts consumption, which impacts nutrition and, ultimately, human health,” Halpern, who is also an associate at the UCSB-based National Center for Ecological Analysis and Synthesis, told summit participants. “The goal is to link, from start to finish, how changes in the marine environment affect human health. It’s an area that is so big, we welcome your collaboration.”
Speaking about fisheries reform and the potential global benefits — in food production, economics and conservation — of recovering wild fisheries, UCSB’s Christopher Costello was optimistic about what progress can be made.
“This is one of these rare environmental challenges where the triple bottom line really is possible,” said Costello, a professor of environmental and resource economics at the Bren School and co-founder, with Gaines, of UCSB’s Sustainable Fisheries Group. “There is almost always some tradeoff between the economy and the environment but that’s not really true in fisheries. They’re pretty well aligned and I think that makes for a pretty compelling story. And I think it also suggests we ought to do something.
“Cross-disciplinary collaborations are really essential to getting this stuff right,” added Costello, lead principal investigator for the Food from the Sea project, echoing the spirit of the day. “Putting all these things together with the human health side and other dimensions can help provide a much richer picture of what we ought to do and what the consequences of those actions are likely to be.”
Also presenting at the summit were Bren School’s Hunter Lenihan, director of the new Sustainable Aquaculture Research Center; Lisa Levin, of UC San Diego’s Scripps Institution of Oceanography; Amro Hamdoun, also of Scripps; Alan Hastings, of UC Davis; Marc Mangel, of UC Santa Cruz, and director of the Center for Stock Assessment Research; and Read Porter, a senior attorney with the Environmental Law Institute.

Contact Info: 

Shelly Leachman
(805) 893-8726
shelly.leachman@ucsb.edu
Office of Public Affairs and Communications
University of California, Santa Barbara
Santa Barbara, CA 93106-2100

Topics: 

18 February 2015

A good night's sleep keeps your stem cells young

© Michael Milsom, DKFZ
Caption: After waking up the hematopoietic stem cells, bone
marrow of normal mice (left) is packed with blood cells
whereas the bone marrow of Fanconi mice is severely
depleted, the blood cells have been replaced by fat cells. 
As we age, the stem cells in all tissues of our body are depleted or fail to function efficiently. This is what drives the age-associated decline in tissue function and the onset of age-related diseases such as cancer. The loss of stem cells is thought to be predominantly driven by accumulative damage to the DNA of stem cells. However, the source of this DNA damage in stem cells has previously been unclear. In a study just published in the journal Nature, scientists at the Deutsches Krebsforschungszentrum (DKFZ) Heidelberg and at the Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH) have uncovered that environmental stress is a major factor in driving DNA damage in adult hematopoietic stem cells. Repeated exposure to such stress causes accelerated tissue aging and probably cancer.

Under normal conditions, many of the different types of tissue-specific adult stem cells, including hematopoietic stem cells, exist in a state or dormancy where they rarely divide and have very low energy demands. "Our theory was that this state of dormancy protected hematopoietic stem cells from DNA damage and therefore protects them from premature aging," says Dr. Michael Milsom, leader of the study.

However, under conditions of stress, such as during chronic blood loss or infection, hematopoietic stem cells are driven into a state of rapid cell division in order to produce new blood cells and repair the damaged tissue. "It's like forcing you out of your bed in the middle of the night and then putting you into a sports car and asking you to drive as fast as you can around a race circuit while you are still half asleep," explains Milsom. "The stem cells go from a state of rest to very high activity within a short space of time, requiring them to rapidly increase their metabolic rate, synthesize new DNA and coordinate cell division. Suddenly having to simultaneously execute these complicated functions dramatically increases the likelihood that something will go wrong."

Indeed, experiments described in the study show that the increased energy demands of the stem cells during stress result in elevated production of reactive metabolites that can directly damage DNA. If this happens at the same time that the cell is trying to replicate its DNA, then this can cause either the death of the stem cell, or potentially the acquisition of mutations that may cause cancer.

Normal stem cells can repair the majority of this stress-induced DNA damage, but the more times you are exposed to stress, the more likely it is that a given stem cell will inefficiently repair the damage and then die or become mutated and act as a seed in the development of leukemia. "We believe that this model perfectly explains the gradual accumulation of DNA damage in stem cells with age and the associated reduction in the ability of a tissue to maintain and repair itself as you get older," Milsom adds.

In addition, the study goes on to examine how this stress response impacts on a mouse model of a rare inherited premature aging disorder that is caused by a defect in DNA repair. Patients with Fanconi anemia suffer a collapse of their blood system and have an extremely high risk of developing cancer. Mouse models of Fanconi anemia have exactly the same DNA repair defect as found in human patients but the mice never spontaneously develop the bone marrow failure observed in nearly all patients.

"We felt that stress induced DNA damage was the missing ingredient that was required to cause hematopoietic stem cell depletion in these mice," says Milsom. When Fanconi anemia mice were exposed to stimulation mimicking a prolonged viral infection, they were unable to efficiently repair the resulting DNA damage and their stem cells failed. In the same space of time that normal mice showed a gradual decline in hematopoietic stem cell numbers, the stem cells in Fanconi anemia mice were almost completely depleted, resulting in bone marrow failure and an inadequate production of blood cells to sustain life.

"This perfectly recapitulates what happens to Fanconi anemia patients and now gives us an opportunity to understand how this disease works and how we might better treat it," commented Milsom.

Prof. Dr. Andreas Trumpp, director of HI-STEM and head of the Division of Stem Cells and Cancer at the DKFZ believes that this work is a big step towards understanding a range of age-related diseases. "The novel link between physiologic stress, mutations in stem cells and aging is very exciting," says Trumpp, a co-author of the study. "By understanding the mechanism via which stem cells age, we can start to think about strategies to prevent or at least reduce the risk of damaged stem cells which are the cause of aging and the seed of cancer."

Dagmar Walter, Amelie Lier, Anja Geiselhart, Frederic B. Thalheimer, Sina Huntscha, Mirko C. Sobotta, Bettina Moehrle, David Brocks, Irem Bayindir, Paul Kaschutnig, Katja Muedder, Corinna Klein, Anna Jauch, Timm Schroeder, Hartmut Geiger, Tobias P. Dick, Tim Holland-Letz, Peter Schmezer, Steven W. Lane, Michael A. Rieger, Marieke A. G. Essers, David A. Williams, Andreas Trumpp und Michael D. Milsom: Exit from dormancy provokes DNA damage-induced attrition in haematopoietic stem cells. Nature 2015, DOI: 10.1038/nature14131



The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) with its more than 3,000 employees is the largest biomedical research institute in Germany. At DKFZ, more than 1,000 scientists investigate how cancer develops, identify cancer risk factors and endeavor to find new strategies to prevent people from getting cancer. They develop novel approaches to make tumor diagnosis more precise and treatment of cancer patients more successful. The staff of the Cancer Information Service (KID) offers information about the widespread disease of cancer for patients, their families, and the general public. Jointly with Heidelberg University Hospital, DKFZ has established the National Center for Tumor Diseases (NCT) Heidelberg, where promising approaches from cancer research are translated into the clinic. In the German Consortium for Translational Cancer Research (DKTK), one of six German Centers for Health Research, DKFZ maintains translational centers at seven university partnering sites. Combining excellent university hospitals with high-profile research at a Helmholtz Center is an important contribution to improving the chances of cancer patients. DKFZ is a member of the Helmholtz Association of National Research Centers, with ninety percent of its funding coming from the German Federal Ministry of Education and Research and the remaining ten percent from the State of Baden-Württemberg.

Contact:

Dr. Stefanie Seltmann
Head of Press and Public Relations
German Cancer Research Center
Im Neuenheimer Feld 280
D-69120 Heidelberg
T: +49 6221 42 2854
F: +49 6221 42 2968
presse@dkfz.de

Dr. Sibylle Kohlstädt
Press and Public Relations
German Cancer Research Center
Im Neuenheimer Feld 280
D-69120 Heidelberg
T: +49 6221 42 2843
F: +49 6221 42 2968
Email: presse@dkfz.de

12 February 2015

An Ocean of Plastic


A new report by the NCEAS Marine Debris Working Group at UCSB calculates the magnitude of plastic waste going into the ocean

A new report estimates the amount of plastic entering the ocean from land, but the amount reaching the ocean floor is unknown.
Photo Credit:
iStock © fergregory


(Santa Barbara, Calif.) — Ocean currents have been carrying floating debris into all five of the world’s major oceanic gyres for decades. The rotating currents of these so-called “garbage patches” create vortexes of trash, much of it plastic. However, exactly how much plastic is making its way into the world’s oceans and from where it originates has been a mystery — until now.

A new study published today in the journal Science, quantifies the input of plastic waste from land into the ocean and offers a roadmap for developing ocean-scale solutions to the problem of plastic marine pollution. The research was conducted by a scientific working group at UC Santa Barbara’s National Center for Ecological Analysis and Synthesis (NCEAS) with support from the Washington, D.C.-based Ocean Conservancy. To conduct the research, lead author Jenna Jambeck, an environmental engineer at the University of Georgia, coordinated contributions from experts in oceanography, waste management and plastics materials science. 

The study found that more than 4.8 million metric tons of plastic waste enters the oceans from land each year, and that figure may be as high as 12.7 million metric tons. That’s one to three orders of magnitude greater than the reported mass of plastic floating in the oceans. A metric ton is equivalent to 1,000 kilograms or 2,205 pounds.

“Using the average density of uncompacted plastic waste, 8 million metric tons — the midpoint of our estimate — would cover an area 34 times the size of Manhattan ankle-deep in plastic waste,” said co-author Roland Geyer, an associate professor at UCSB’s Bren School of Environmental Science & Management. “Eight million metric tons is a vast amount of material by any measure. It is how much plastic was produced worldwide in 1961.”

Previous studies have documented the impact of plastic debris on more than 660 marine species — from the smallest of zooplankton to the largest whales, including fish destined for the seafood market — but none have quantified the worldwide amount entering the ocean from land. “This is the first time people have connected the dots in a quantifiable way,” said Jambeck. 
According to the study, countries with coastal borders — 192 in all — discharge plastic into the world’s oceans with the largest quantities estimated to come from a relatively small number of middle-income, rapidly developing countries. In fact, the investigators found that the top 20 countries accounted for 83 percent of the mismanaged plastic waste available to enter the ocean. They went on to say that reducing the amount of this waste by 50 percent would result in a nearly 40 percent decline in inputs of plastic to the ocean.
“Large-scale removal of plastic marine debris is not going to be cost-effective and quite likely simply unfeasible,” said Geyer. “This means that we need to prevent plastic from entering the oceans in the first place through better waste management, more reuse and recycling, better product design and material substitution.”
Knowing how much plastic is going into the ocean is just one part of the puzzle. Millions of metric tons reach the oceans, yet researchers are finding between 6,350 and 245,000 metric tons floating on the surface — a mere fraction of the total. This discrepancy is the subject of ongoing research.
“Right now, we’re mainly measuring plastic that floats,” said study co-author Kara Lavender Law, a research professor at the Massachusetts-based Sea Education Association. “There is a lot of plastic sitting on the bottom of the ocean and on beaches worldwide.”
The NCEAS working group forecasts that the cumulative impact to the oceans could be as high as 155 million metric tons by 2025. However, the planet will not reach global “peak waste” before 2100, according to World Bank calculations. “We’re being overwhelmed by our waste,” Jambeck said.
“The numbers are staggering, but as the group points out, the problem is not insurmountable,” said NCEAS Director Frank Davis, who is also a professor at UCSB’s Bren School. “The researchers suggest achievable solutions that could reverse the alarming trend in plastics being dumped into our oceans.”
Among them, according to the study, are waste reduction and “downstream” waste management strategies such as expanded recovery systems and extended producer responsibility. According to the researchers, while infrastructure is being built in developing nations, “industrialized countries can take immediate action by reducing waste and curbing the growth of single-use plastic.”

Contact Info: 

Julie Cohen
julie.cohen@ucsb.edu
(805) 893-7220
- See more at: http://www.news.ucsb.edu/2015/014985/ocean-plastic#sthash.XY2nV9VN.dpuf

06 February 2015

MIT News: New source of cells for modeling malaria

Liver cells derived from stem cells can be infected with malaria and used to test potential drugs
MIT researchers engineered liver-like cells that can be infected with several strains of the parasite that causes malaria, including Plasmodium falciparum (top row) and Plasmodium berghei (bottom row). The red stain reveals parasite infection.


CAMBRIDGE, MA -- In 2008, the World Health Organization announced a global effort to eradicate malaria, which kills about 800,000 people every year. As part of that goal, scientists are trying to develop new drugs that target the malaria parasite during the stage when it infects the human liver, which is
MIT researchers engineered liver-like cells that can be infected with several strains of the parasite that causes malaria, including Plasmodium falciparum (top row) and Plasmodium berghei (bottom row). The red stain reveals parasite infection. Courtesy of the researchers
crucial because some strains of malaria can lie dormant in the liver for several years before flaring up.
A new advance by MIT engineers could aid in those efforts: The researchers have discovered a way to grow liver-like cells from induced pluripotent stem cells. These cells can be infected with several strains of the malaria parasite and respond to existing drugs the same way that mature liver cells taken from human donors do.
Such cells offer a plentiful source for testing potential malaria drugs because they can be made from skin cells. New drugs are badly needed, since some forms of the malaria parasite have become resistant to existing treatments, says Sangeeta Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology (HST) and Electrical Engineering and Computer Science at MIT.
“Drug resistance is emerging that we are continually chasing. The thinking behind the call to eradication is that we can’t be chasing resistance and distributing bed nets to protect from mosquitoes forever. Ideally, we would rid ourselves of the pathogen entirely,” says Bhatia, who is also a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science (IMES).
These cells, described in the Feb. 5 online issue of Stem Cell Reports, could also allow scientists to test drugs on cells from people with different genetic backgrounds, who may respond differently to malaria infection and treatment.
The paper’s lead author is Shengyong Ng, a graduate student in MIT’s Department of Biological Engineering and IMES. Other authors of the paper are former IMES postdoc Robert Schwartz; MIT research scientist Sandra March; IMES research technician Ani Galstian; HST graduate students Nil Gural and Jing Shan; former IMES research technician Mythili Prabhu; and Maria Mota, a researcher at the Instituto de Medicina Molecular in Portugal.

Modeling infection
Until now, malaria researchers have not had many reliable ways to test new drugs in liver tissue. “What’s historically been done is people have tried to make do with the systems that were available,” Bhatia says.
Those systems include testing drugs in cancerous liver cells or in mice infected with a rodent-specific version of the malaria parasite. However, cancerous cells divide much more frequently than normal adult liver cells, and are missing some of the genes required for drug metabolism. The mouse model is not ideal because the rodent version of malaria is different from the human one, so drugs that are successful in mice don’t always work in humans.
In 2013, Bhatia and colleagues showed that they could mode malaria infection in adult liver cells, known as hepatocytes, taken from human donors. However, this generates only a limited supply from each donor, and not all of the cells work well for drug studies.
The researchers then turned to induced pluripotent stem cells. These immature cells can be generated from human skin cells by adding several genes known as reprogramming factors. Once the cells are reprogrammed, they can be directed to form differentiated adult cells by adding specific growth factors.
To create liver cells, the researchers added a series of growth factors, including hepatocyte growth factor. Working with Charles Rice of Rockefeller University and Stephen Duncan of the Medical College of Wisconsin, Bhatia’s lab generated these cells in 2012 and used them to model infection of hepatitis C. However, these cells, known as hepatocyte-like cells, did not seem to be as mature as real adult liver cells.
In the new study, the MIT team found that these cells could be infected with several strains of malaria, but did not have the same drug responses as adult liver cells. In particular, they were not sensitive to primaquine, which works only if cells have a certain set of drug-metabolism enzymes found in mature liver cells. This is important because primaquine is one of only two drugs approved to treat liver-stage malaria, and many of the drugs now in development are based on primaquine.
To induce the cells to become more mature and turn on these metabolic enzymes, the researchers added a molecule they had identified in a previous study. This compound, which the researchers call a “maturin,” stimulated the cells to turn on those enzymes, which made them sensitive to primaquine treatment.

Toward better drugs
The MIT team is now working with the nonprofit foundation Medical Malaria Ventures to test about 10 potential malaria drugs that are in the pipeline, first using adult donor liver cells and then the hepatocyte-like cells generated in this study.
These cells could also prove useful to help identify new drug targets. In this study, the researchers found that the liver-like cells can be infected with malaria when they are still in the equivalent of fetal stages of development, when they become cells known as hepatoblasts, which are precursors to hepatocytes.
In future studies, the researchers plan to investigate which genes get turned on at the point when the cells become susceptible to infection, which may suggest new targets for malaria drugs. They also hope to compare the genes needed for malaria infection with those needed for hepatitis infection, in hopes of identifying common pathways to target for both diseases.
The research was funded by the Bill and Melinda Gates Foundation; the Singapore Agency for Science, Technology and Research; and the Howard Hughes Medical Institute.

Written by Anne Trafton, MIT News Office



Contact: Sarah McDonnell, MIT News Office
E: s_mcd@mit.edu, T: 617-253-8923
Massachusetts Institute of Technology, 77 Massachusetts Avenue Building 11-400, Cambridge, MA 02139-4307 United States

02 February 2015

The Games People Play


UCSB’s new Center for Digital Games Research takes a multidisciplinary approach to the study and design of digital media and games

(Santa Barbara, Calif.) — Want to add some adventure to your daily run? Try jogging through a zombie apocalypse with “Zombies, Run!” Or sign up with a virtual personal trainer who will be available 24/7 and won’t cost an arm and a leg with Nike+ Kinect Training.
Debra Liebermann,
Photo Credit: Spencer Bruttig
Video games have come a long way since Pac-Man and Space Invaders. As technology has advanced by leaps and bounds so have storylines, graphics and user interfaces. Once the province of adolescent boys, this form of digital media now appeals to people of both genders and of all ages. What’s more, it has found applications in a host of areas such as K-12 learning, health education in hospitals and clinics, physical therapy and rehabilitation at home, psychotherapy and counseling, workplace training, op-ed journalism and crowdsourcing for scientific discovery.
The impact of video games — and digital media in general — as well as their boundless potential to engage and entertain in ways that enrich people’s lives, is the focus of the newly established Center for Digital Games Research at UC Santa Barbara.
Erica Biely, Photo Credit: Spencer Bruttig
“Many of our affiliated faculty members investigate players’ cognitive and emotional responses to digital media and games, and how these responses can be used to advance player knowledge, skills, attitudes and behavior as a way to move design and implementation forward,” said Debra Lieberman, Ph.D., the center’s director and a researcher at UCSB’s Institute for Social, Behavioral, and Economic Research. Supported by seed money from the Robert Wood Johnson Foundation, the Center for Digital Games Research studies digital media and games from a multidisciplinary perspective. Faculty affiliates bring a wide range of expertise in areas such as human-computer interaction, virtual environments, simulations, social networks, data mining, interactive storytelling and narrative, media neuroscience, and behavioral health.
“Our research contributes to the evidence-based design of digital media and games to improve their quality and effectiveness and to serve the needs and abilities of end users,” said Lieberman, who is also a lecturer in UCSB’s Department of Communication. Her own research is focused on processes of learning, motivation and behavior change with interactive media and games, with special interests in the design of games for health and learning.

Lieberman’s current grant from the Robert Wood Johnson Foundation follows her 2007 award
that established at UCSB a six-year, $8.25-million national program called Health Games Research, with
Lieberman serving as director. She and her team provided scientific leadership in the emerging health
games field and funded 21 research projects across the country that studied the design and effectiveness
of health games.
“The field has grown enormously, and the research has, too,” said Lieberman. “UCSB saw an
opportunity to continue our work in a way that would include the university’s faculty from many
academic disciplines and would bring together their wide range of research and development expertise.
The Robert Wood Johnson Foundation liked the idea and provided start-up funding to help us establish
the center.”
“As we work to build a Culture of Health, digital games — which are ingrained in the daily lives
of Americans across the ages — have a role in helping us make healthier decisions and foster healthier
lifestyles,” said Paul Tarini, Robert Wood Johnson Foundation senior program officer. “We have good
evidence that games can be used to improve health. The Center for Digital Games Research will put that
knowledge to work, guiding gamers and designers in developing the next generation of health games.”
The center at UCSB is novel in its research approach. “We wanted the word ‘research’ in the
name of our center because it is fundamental to what we do. Building an evidence base that leads to
effective principles of game design is essential to creating interactive media and games that will engage,
entertain and inspire people and will immerse them in compelling and impactful virtual experiences.”
UCSB’s center is novel also in its interdisciplinary nature. Affiliated faculty members — 30 so
far — cut a broad swath across campus, with home departments in the physical and biological sciences,
computer and engineering sciences, social and behavioral sciences and the arts and humanities. “We now
have a wide range of expertise and initiatives,” Lieberman continued. “And we’re working with a variety
of digital media.”
Take Frank Doyle’s research, for example. The professor and chair of chemical engineering is
working with his team to develop an artificial pancreas as a way of delivering insulin to individuals who
have Type-1 diabetes. “This is a profound change in their treatment because they’re letting technology
manage their disease,” Doyle said.
But what do video games have to do with an artificial pancreas?
DIGITAL GAMES RESEARCH 3-3-3
technology. There’s a profound link between what we’re doing and the behavioral aspects that come out
of things like digital games research.”
Other research projects connected to the Center for Digital Games Research are looking at topics
such as the changes that occur in the brain when people are using media; the design of cellphone sensors
that can contribute to health behavior change and health self-monitoring; and even the use of tablet games
for learning English.
In Matthew Turk’s Four Eyes Lab at UCSB, research focuses on interactive technologies using
sensing and other techniques to communicate with people in ways that normal computing doesn’t. “Our
biggest overlap with the center,” the professor of computer science explained, “is to introduce new kinds
of technologies into the gaming environment — sensing people, understanding their identity, their
motion, their activities, and also sensing the world, building models of the world so we can bring the
physical space into the gaming scenario.”
A good example of that is augmented reality, continued Turk, who is also a faculty member in the
campus’s Media Arts and Technology Program. “In augmented reality we’re dealing with mixing
computer-generated imagery with some sort of display of reality, maybe on a mobile device or a
computer screen.”
The same augmented-reality technologies that make video games more, well, realistic have other
applications as well. Remote collaboration — people trying to work on things together when those things
involve the physical space around them — is only one example. “Take for example a repair task or
something similar. It doesn’t work very well with Skype or some 2-D-oriented conferencing,” Turk
explained. “But when we can model the local world and let people interact spatially rather than just
through 2-D imagery, something that’s very relevant to gaming could be transformational for video-based
communications.”
It could also transform remote medicine and the ability of a physician in, say, Baltimore to lend
medical expertise to a patient in South Africa. “That’s an area where the gaming technologies have a real
clear use in lots of areas in the world,” Turk said.
In addition to conducting research and development, the Center for Digital Games Research
maintains an online searchable Health Games Database that provides information about hundreds of
health games and hundreds of related publications, resources, organizations and events. “The database has
been widely used over the past several years and we have received very positive feedback from our users,
who appreciate having a comprehensive collection of games-related resources assembled in one place that
is easy to use and navigate,” said Erica Biely, the center’s associate director.
“All these pieces — the database, the broad multidisciplinary research, the application of research
to advance the design of media, games and related technologies — come together in a center that is
building our understanding of the ways interactive media and games affect our lives today and how we
can improve them and innovate with them in the future,” Lieberman said.

Note to editors: Debra Lieberman is available at debra.lieberman@ucsb.edu or (805) 893-7571. Erica
Biely is available at erica.biely@ucsb.edu or (805) 893-7787.

 Andrea Estrada
(805) 893-4620
andrea.estrada@ucsb.edu
George Foulsham
(805) 893-3071
george.foulsham@ucsb.edu
February 2, 2015