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ELIGIBILITY • Researchers who received their first advanced degree, such as the PhD, in 2005 or

more recently are invited to submit an entry.

AWARD • In addition to the USD 10,000 personal honorarium, the award recipient will present

a research seminar at the symposium and, before the seminar, a separate introductory

lecture on neurodegenerative disease.

• Also at the symposium, Prof. Pietro De Camilli, Yale School of Medicine, will give the Sprague

Lecture, and Prof. Beth Stevens, Harvard Medical School, will give the Adler Lecture.

SUBMISSION • Applicants should submit a single PDF file with a one-page description of their contribution to

neurodegenerative research, full curricula vitae, and names of three references.

• The deadline for submissions is December 1, 2018 to [email protected].

More information can be found at www.med.upenn.edu/ins.

R I S I N G S T A R A W A R D

IN NEURODEGENERATIVE RESEARCH

CALL FOR SUBMISSIONS

The Mahoney Institute for Neurosciences (MINS) at the University of Pennsylvania is pleased to announce an international

call for submissions for the annual Rising Star Award in neuroscience research. To highlight the ÒYear of Neurodegenerative

ResearchÓ on PennÕs campus, the award honors a young researcher for outstanding contributions to neurodegenerative

research with a USD 10,000 personal honorarium at the MINS 35th Annual Retreat and Symposium on April 3, 2019.

“Neurodegenerative disorders are major health problems for the elderly, and there are currently no treatments for any of

these diseases,” said Virginia Lee, PhD, director of Penn’s Center for Neurodegenerative Disease and a MINS faculty member.

“I am proud that there is a large research community at Penn, including MINS, at the forefront of research elucidating the etiology

and pathogenesis of these devastating disorders. We look forward to honoring and facilitating a young researcher to enhance our

understanding of age-related neurodegeneration and to advance future therapies.”

© 2018 University of Pennsylvania - MINS

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Decoding disease.

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WILL DICHTEL

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Chemist Will Dichtel, Northwestern University, is the 2018 recipient of the Cottrell Frontiers in Research Excellenceand Discovery (FRED) Award from Research Corporation for Science Advancement. His work addresses the mostimportant contemporary challenges at the interface of organic chemistry and materials science. Specifically, the$250,000 FRED Award goes to support Dichtel’s pioneering eforts to develop new methods to polymerize diversemonomers into ordered, two-dimensional polymers with unprecedented control of their covalent structure,crystallite size and shape, and higher-order assembly.

The Cottrell FRED Award supports early stages of exceptional, high-risk/high-reward research that may potentiallytransform a field of scientific inquiry. It is presented to highly creative Cottrell Scholars whose ideas and potentialsolutions, though not readily funded by conventional grant programs, address major current challenges in therecipients’ areas of research expertise.

By developing unique perspectives for solving key challenges, Cottrell FRED awardees create new approaches thataccelerate basic science research for the benefit of society.

Since 1994 the Cottrell Scholar program has developed outstanding teacher-scholars recognized by their scientificcommunities for the quality and innovation of their research programs and their academic leadership skills

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Leslie VosshallRockefeller University

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Jared ToettcherPrinceton University

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Sheena JosselynHospital for Sick Children

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APPLY TODAY

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MichelsonPrizes

DEADLINE OCTOBER 29, 2018

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Congratulations

to Johannes Kohl, Ph.D.

Harvard University

AAAS®andScience®are

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Learn more at: www.eppendorf.com/prize

And the Winner Is...Eppendorf & Science Prize for Neurobiology

Congratulations to Johannes Kohl on winning the

2018 Eppendorf & Science Prize for his work on neural

mechanisms underlying parental care. Dr. Kohl’s

research has revealed how a small population of

genetically defined neurons controls the motor,

motivational, hormonal and social aspects of parental

behavior in males and females. These findings provide

a new model for how specific components of a social

behavior are generated at the neural circuit level.

Unravelling the functional architecture of such circuits

will advance our understanding of how the brain

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The annual US$25,000 Eppendorf & Science Prize for

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Johannes Kohl is the 17th recipient of this international

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You could be next to win this prize.

If you are 35 years of age or younger and currently per-

forming neurobiological research, you could be next to

win the 2019 Prize. Deadline for entries is June 15, 2019.

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Neuroscience 2018

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LIFE SCIENCE TECHNOLOGIES

243SCIENCE sciencemag.org/custom-publishing

animal models

Produced by the Science/AAAS Custom Publishing Office

Six years ago, Ping Yehís oncologist told him his Hodgkinís lymphoma was resistant to the standard chemotherapy regimen and he would need a more potent, seven-drug cocktail. The treatment knocked his cancer into remission,

but afterward Yeh needed an ultrasound to check whether the treatment, which can be cardiotoxic in some patients, had damaged his heart.

ìThe treatment could have cured me. Or cured me and killed me,î says Yeh, a nanotechnologist. ìIt was a pretty scary #$%#&�#��#��%��#��#�##��&��#�� &#��#&#�was a better way to test for drug safety.î That seed sprouted into Minneapolis-based StemoniX, which Yeh cofounded in 2014 for the purpose of combining advances in engineering, manufacturing, and human stem cells to develop drug screening and testing platforms with more relevance to human physiology.

Fortunately, Yehís heart was spared. Unfortunately, patients like Yeh encounter toxic or ineffective drugs all too often, because the animal models used to test drugs before they go into patients are imperfect in many ways. Of all the drugs that enter clinical trials, only about 10% go on to be approved (1). The other 90% fail during trialsófor reasons ranging from off-target, undesirable effects and problematic dosing, to low or no # ��#��&��#��#��&��$��

ìThe closer you can get to mimicking the human situation, the better the research is going to be in [terms of] understanding

the fundamental pathology of disease and also in predicting %��#��# ��$��&��#&�%�#��&��Eglen, vice president and general manager of Corning Life Sciences in Boston, Massachusetts.

However, the challenge will be to design models that hold �� #��#&��&&#��%%&��#��#��producing models that give robust, reproducible data, that are predictive of human biology, and that will not greatly increase costs. StemoniX, Corning, and several other companies are coming up with innovative ways to meet that challenge.

Imposing structure on cultures

Culturing methods have continued to improve, and are now yielding 3D cell cultures, spheroids, and even more complex �&��&#��&��#��&#��#��#��&��has led the way in providing researchers with the best surfaces on which to grow these cultures. Now, the company has added a 1,536-well spheroid plate that can work at the highest levels of automated screening. The rounded-bottom wells, which are coated with an ultralow attachment surface, encourage plated cells to aggregate with each other and form a sphere.

ìThat is going to enable researchers to do ultra-high-throughput screening of up to 100,000 compounds per day,î says Eglen. The plates have small well volumes and therefore produce small spheroids that range from 500 to 2,000 cells, but they give reproducible responses that are linear relative to cell number.��&��%��#��&�%%��##�&��#��&��

has used the plates with pancreatic tumor spheroids to identify �� &��#��#��!��#�#��"��%�&��#��2D-cell-cultureñbased screen did not turn up the same inhibitor (2). Corningís own research using known liver toxins on hu-man liver spheroids shows they can be used to screen

Upcoming features

When it comes to mimicking human disease or predicting the

human bodyís response to candidate drugs, traditional laboratory

animal models are woefully inadequate. New technologiesó3D

cell culturing, human induced pluripotent stem cells, and gene

��

reducing animal models. By Kendall Powell

Tissue/Cell Culture: Expression Systems—November 16 DNA/RNA: Improving ChIP Assays—December 7 Next-Generation Sequencing—February 22

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CRISPR gene editing and other techniques are improving and even replacing animal models.

Replacing the replacements:Animal model alternatives


244 SCIENCE sciencemag.org/custom-publishing

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it comes to designing gradients or layering two or more proteins. One such technique, microcontact printing, uses a stamp dipped into protein solution to imprint it onto a culture surface, but lacks precision for :;<=�<=��:��<��=�<�<��;��<�=��proteins. To address those limitations, a trio of academic researchers at ;=��<=��=��;��;��<�=�<��Research (CNRS) dreamt up PRIMO, a contactless and maskless technique for micropatterning, and started up AlvÈole.�

PRIMO is based on light-induced mo-lecular adsorption of proteins (LIMAP) and combines a UV illumination system �<��:��<��;��=��=��=�<=��;�� <�;��:��=�<=��!"��;�=��a micromirror device projector that �=�:;#��=$�< ��; �� -puter onto the surface of culture plates through the microscopeís objective

��=�%��<��;��<=��&�'�( �Glass slides, coverslips, plastic plates, and also hydrogels can

�;��;��<��:�$��$��=��$��)�*+,��=�=�<��<=��=�%��=��:��<��:��:��<:<��:��:��)�-��,�:��<=<�<�;�;��=��<��<=��<=��.��=�� <=��<��the projected UV light in the pattern of choice, the PLPP degrades ��*+%��<=��/��0��$��:;��<=)�,��<��PRIMOís Leonardo software controls the movements of the motorized microscope stage for aligning or shifting patterns. Also, using the softwareís 256 grayscale levels to vary the UV intensity ��;��;��;��=�;�� *+�<��;��=��therefore how much protein adheres to the surface.

For 3D applications, protein micropatterns laid down on a coverslip can be transferred to the surface of a hydrogel, since illuminating hydrogels directly with UV light can change their ;<�<�<�$��;��;�� =��<��:�$�< ��$��<��=��:�$ �;� <�;��;��:��$��<=��:;�<��;�12��=��;�<=��3=��;��;�:��;�� =�<=��:��;<:��=�� )�<��,�<=��;�$��;<�=��=��<=%��;<��<=��measure microtubule growth dynamics in a patient with the neurodegenerative disease Rett syndrome (3)./!�<=��%��:��;�:��;$��<��;�=��:��=��

widths of lines in just a few weeksówith other micropatterning ��=<��<��4�=� =��%0��$��;<�5��;��Manus, operational marketing manager at AlvÈole in Paris.

The system is not well suited to high-throughput imaging or screening yet, says Manus, although the company is working on a ��;�<=��<�� <��:�� ;�=�%�<=�<�<��;��;��;��can use PRIMO to get closer to the in vivo microenvironment by optimizing the signal patterns that their cell cultures experience.

More precise CRISPR modelsGene editing technology is bringing a whole new level of

genetic manipulation to human cell cultures, whether they are transformed cell lines, patient-derived primary cultures, or iPSCs. .�<��;��;��;��<��=�� ;��$�;��$��=�<��;� 4<=��knockout humans yet, technologies like CRISPR/Cas9 allow

compounds for liver toxicity. /.��;$=��<4��<��the ability to better predict the metabolism of drugs before :��<=�� <=��:�<�=�%0��$��*��=��

Corning has developed an-other technology to support the 3D growth of mesenchymal stem cells (MSCs). Researchers would like to develop MSCsóalso known as adult stem cellsóinto individualized, cell-based patient therapies, such as replacements for faulty insulin-producing islet cells in diabetes, for instance. But itís been a challenge growing enough MSCs under pristine conditions to then administer the cells back to the patient. Corningís digestible microcar-rier technology uses an inert,nonanimal-derived polymer to grow the cells in a 3D orientation in solution on the microcar-rierís surface. Then, by adding an enzyme, the microcarrier can be dissolved away to leave just the MSCs for isolation.

Human cell mass production�� =<6��;��/��5��5��0��;��;��'2� <�;7�;��=��

microBrain plates, as well as microBrain 3D spheroid plates, for high-throughput screening that offers precise measurement of human tissue responses. The company chose to focus on brain and heart cells in part because neurotoxicity and cardiotoxicity are the top two reasons why drugs fail for safety reasons during clinical trials. �� <�;7�;��;��;��;�=��=�� <�;��==��

form sarcomeric unit structures like those found in heart mus-cleócomplete with physical markers, correct ion-channel forma-tion, and a unidirectional contraction.

The microBrain 2D and 3D cells are a mix of astrocytes and neurons that form synapses as well as being rudimentary neural networks. The 2D culture is key for measuring visual changes in the cells, such as neural projections. The 3D spheroid cultures are harder to visualize, but they exhibit spontaneous, synchro-=��=��;��;<=�%��<��=��=�<��<��$��;��=��;��;��;��:=��<=8��=��;<=��< <�;�$%��;�< $�$��contractions can be quantitatively assayed for drug responses, such as arrhythmias./�� :�;��%0��4=��9��%��=�� =<6��

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Microenvironment mimicsMicropatterning allows researchers to add sophistication to cul-

tures, for example, by manipulating signaling molecules or growth ��;��<=��:��<��:��;=��;��;�<�=��%��<�� ;��:�;< �=-��=�;��<=8��=��<�=�<=��=�<=��5=< �� .�<�� <�;:��;=<=��=<��=��<��;�

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Researchers would like to develop MSCsóalso

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cell-based patient therapies, such as

replacements for faulty insulin-producing

islet cells in diabetes.

Mesenchymal stem cells


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References5��:�� I��et al., Nat. Biotech��32��64;=5�1*4562��

*��$��I�et al., Oncogene 37��6,A*;6,B6�1*45B2C��@�54�54,B/� �

� H65,BB�45B�4*=A�=�

,��+G D��G�et al., Hum. Mol. Genetics. 25��56E;5=A�1*45E2C��

� ��@�54�540,/��/��6E6��

Kendall Powell is a freelance science writer based in Lafayette, Colorado.

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