Tag Archives: molecular biology

Teaching molecular and synthetic biology in grades K-12

This* story actually started in 2018 with an August 1, 2018 Harvard University news release (h/t Aug. 1, 2018 news item on phys.org) by Leslie Brownell announcing molecular and synthetic biology educational kits that been tested in the classroom. (In 2019, a new kit was released but more about that later.)

As biologists have probed deeper into the molecular and genetic underpinnings of life, K-12 schools have struggled to provide a curriculum that reflects those advances. Hands-on learning is known to be more engaging and effective for teaching science to students, but even the most basic molecular and synthetic biology experiments require equipment far beyond an average classroom’s budget, and often involve the use of bacteria and other substances that can be difficult to manage outside a controlled lab setting.

Now, a collaboration between the Wyss Institute at Harvard University, MIT [Massachusetts Institute of Technology], and Northwestern University has developed BioBits, new educational biology kits that use freeze-dried cell-free (FD-CF) reactions to enable students to perform a range of simple, hands-on biological experiments. The BioBits kits introduce molecular and synthetic biology concepts without the need for specialized lab equipment, at a fraction of the cost of current standard experimental designs. The kits are described in two papers published in Science Advances [2018].

“The main motivation in developing these kits was to give students fun activities that allow them to actually see, smell, and touch the outcomes of the biological reactions they’re doing at the molecular level,” said Ally Huang, a co-first author on both papers who is an MIT graduate student in the lab of Wyss Founding Core Faculty member Jim Collins, Ph.D. “My hope is that they will inspire more kids to consider a career in STEM [science, technology, engineering, and math] and, more generally, give all students a basic understanding of how biology works, because they may one day have to make personal or policy decisions based on modern science.”

Synthetic and molecular biology frequently make use of the cellular machinery found in E. coli bacteria to produce a desired protein. But this system requires that the bacteria be kept alive and contained for an extended period of time, and involves several complicated preparation and processing steps. The FD-CF reactions pioneered in Collins’ lab for molecular manufacturing, when combined with innovations from the lab of Michael Jewett, Ph.D. at Northwestern University, offer a solution to this problem by removing bacteria from the equation altogether.

“You can think of it like opening the hood of a car and taking the engine out: we’ve taken the ‘engine’ that drives protein production out of a bacterial cell and given it the fuel it needs, including ribosomes and amino acids, to create proteins from DNA outside of the bacteria itself,” explained Jewett, who is the Charles Deering McCormick Professor of Teaching Excellence at Northwestern University’s McCormick School of Engineering and co-director of Northwestern’s Center for Synthetic Biology, and co-corresponding author of both papers. This collection of molecular machinery is then freeze-dried into pellets so that it becomes shelf-stable at room temperature. To initiate the transcription of DNA into RNA and the translation of that RNA into a protein, a student just needs to add the desired DNA and water to the freeze-dried pellets.

The researchers designed a range of molecular experiments that can be performed using this system, and coupled each of them to a signal that the students can easily detect with their sense of sight, smell, or touch. The first, called BioBits Bright, contains six different freeze-dried DNA templates that each encode a protein that fluoresces a different color when illuminated with blue light. To produce the proteins, students simply add these DNA templates and water to the FD-CF machinery and put the reactions in an inexpensive incubator (~$30) for several hours, and then view them with a blue light illuminator (~$15). The students can also design their own experiments to produce a desired collection of colors that they can then arrange into a visual image, a bit like using a Light Brite ©. “Challenging the students to build their own in vitro synthetic programs also allows educators to start to talk about how synthetic biologists might control biology to make important products, such as medicines or chemicals,” explained Jessica Stark, an NSF Graduate Research Fellow in the Jewett lab at Northwestern University who is co-first author on both papers.

An expansion of the BioBits Bright kit, called BioBits Explorer, includes experiments that engage the senses of smell and touch and allow students to probe their environment using designer synthetic biosensors. In the first experiment, the FD-CF reaction pellets contain a gene that drives the conversion of isoamyl alcohol to isoamyl acetate, a compound that produces a strong banana odor. In the second experiment, the FD-CF reactions contain a gene coding for the enzyme sortase, which recognizes and links specific segments of proteins in a liquid solution together to form a squishy, semi-solid hydrogel, which the students can touch and manipulate. The third module uses another Wyss technology, the toehold switch sensor, to identify DNA extracted from a banana or a kiwi. The sensors are hairpin-shaped RNA molecules designed such that when they bind to a “trigger” RNA, they spring open and reveal a genetic sequence that produces a fluorescent protein. When fruit DNA is added to the sensor-containing FD-CF pellets, only the sensors that are designed to open in the presence of each fruit’s RNA will produce the fluorescent protein.

The researchers tested their BioBits kits in the Chicago Public School system, and demonstrated that students and teachers were able to perform the experiments in the kits with the same success as trained synthetic biology researchers. In addition to refining the kits’ design so that they can one day provide them to classrooms around the world, the authors hope to create an open-source online database where teachers and students can share their results and ideas for ways to modify the kits to explore different biological questions.

“Synthetic biology is going to be one of the defining technologies of the century, and yet it has been challenging to teach the fundamental concepts of the field in K-12 classrooms given that such efforts often require expensive, complicated equipment,” said Collins, who is a co-corresponding author of both papers and also the Termeer Professor of Medical Engineering & Science at MIT. “We show that it is possible to use freeze-dried, cell-free extracts along with freeze-dried synthetic biology components to conduct innovative educational experiments in classrooms and other low-resource settings. The BioBits kits enable us to expose young kids, older kids, and even adults to the wonders of synthetic biology and, as a result, are poised to transform science education and society.

“All scientists are passionate about what they do, and we are frustrated by the difficulty our educational system has had in inciting a similar level of passion in young people. This BioBits project demonstrates the kind of out-of-the-box thinking and refusal to accept the status quo that we value and cultivate at the Wyss Institute, and we all hope it will stimulate young people to be intrigued by science,” said Wyss Institute Founding Director Donald Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School (HMS) and the Vascular Biology Program at Boston Children’s Hospital, as well as Professor of Bioengineering at Harvard’s John A. Paulson School of Engineering and Applied Sciences (SEAS). “It’s exciting to see this project move forward and become available to biology classrooms worldwide and, hopefully some of these students will pursue a path in science because of their experience.”

Additional authors of the papers include Peter Nguyen, Ph.D., Nina Donghia, and Tom Ferrante from the Wyss Institute; Melissa Takahashi, Ph.D. and Aaron Dy from MIT; Karen Hsu and Rachel Dubner from Northwestern University; Keith Pardee, Ph.D., Assistant Professor at the University of Toronto; and a number of teachers and students in the Chicago school system including: Mary Anderson, Ada Kanapskyte, Quinn Mucha, Jessica Packett, Palak Patel, Richa Patel, Deema Qaq, Tyler Zondor, Julie Burke, Tom Martinez, Ashlee Miller-Berry, Aparna Puppala, Kara Reichert, Miriam Schmid, Lance Brand, Lander Hill, Jemima Chellaswamy, Nuhie Faheem, Suzanne Fetherling, Elissa Gong, Eddie Marie Gonzales, Teresa Granito, Jenna Koritsaris, Binh Nguyen, Sujud Ottman, Christina Palffy, Angela Patel, Sheila Skweres, Adriane Slaton, and TaRhonda Woods.

This research was supported by the Army Research Office, the National Science Foundation, the Air Force Research Laboratory Center of Excellence Grant, The Defense Threat Reduction Agency Grant, the David and Lucile Packard Foundation, the Camille Dreyfus Teacher-Scholar Program, the Wyss Institute at Harvard University, the Paul G. Allen Frontiers Group, The Air Force Office of Scientific Research, and the Natural Sciences and Engineering Council of Canada. [emphases mine]

Well, that list of funding agencies is quite interesting. The US Army and Air Force but not the Navy? As for what the Natural Sciences and Engineering Council of Canada is doing on that list, I can only imagine why.

This is what they were doing in 2018,

Now for the latest update, a May 7, 2019 news item on phys.org announces the BioBits Kits have been expanded,

How can high school students learn about a technology as complex and abstract as CRISPR? It’s simple: just add water.

A Northwestern University-led team has developed BioBits, a suite of hands-on educational kits that enable students to perform a range of biological experiments by adding water and simple reagents to freeze-dried cell-free reactions. The kits link complex biological concepts to visual, fluorescent readouts, so students know—after a few hours and with a single glance—the results of their experiments.

A May 7, 2019 Northwestern University news release (also on EurekAlert and received via email) by Amanda Morris, which originated the news item, provides more details,

After launching BioBits last summer, the researchers are now expanding the kit to include modules for CRISPR [clustered regularly interspaced short palindromic repeats] and antibiotic resistance. A small group of Chicago-area teachers and high school students just completed the first pilot study for these new modules, which include interactive experiments and supplementary materials exploring ethics and strategies.

“After we unveiled the first kits, we next wanted to tackle current topics that are important for society,” said Northwestern’s Michael Jewett, principal investigator of the study. “That led us to two areas: antibiotic resistance and gene editing.”

Called BioBits Health, the new kits and pilot study are detailed in a paper published today (May 7 [2019]) in the journal ACS Synthetic Biology.

Jewett is a professor of chemical and biological engineering in Northwestern’s McCormick School of Engineering and co-director of Northwestern’s Center for Synthetic Biology. Jessica Stark, a graduate student in Jewett’s laboratory, led the study.

Test in a tube

Instead of using live cells, the BioBits team removed the essential cellular machinery from inside the cells and freeze-dried them for shelf stability. Keeping cells alive and contained for an extended period of time involves several complicated, time-consuming preparation and processing steps as well as expensive equipment. Freeze-dried cell-free reactions bypass those complications and costs.

“These are essentially test-tube biological reactions,” said Stark, a National Science Foundation graduate research fellow. “We break the cells open and use their guts, which still contain all of the necessary biological machinery to carry out a reaction. We no longer need living cells to demonstrate biology.”

This method to harness biological systems without intact, living cells became possible over the last two decades thanks to multiple innovations, including many in cell-free synthetic biology by Jewett’s lab. Not only are these experiments doable in the classroom, they also only cost pennies compared to standard high-tech experimental designs.

“I’m hopeful that students get excited about engineering biology and want to learn more,” Jewett said.

Conquering CRISPR

One of the biggest scientific breakthroughs of the past decade, CRISPR (pronounced “crisper”) stands for Clustered Regularly Interspaced Short Palindromic Repeats. The powerful gene-editing technology uses enzymes to cut DNA in precise locations to turn off or edit targeted genes. It could be used to halt genetic diseases, develop new medicines, make food more nutritious and much more.

BioBits Health uses three components required for CRISPR: an enzyme called the Cas9 protein, a target DNA sequence encoding a fluorescent protein and an RNA molecule that targets the fluorescent protein gene. When students add all three components — and water — to the freeze-dried cell-free system, it creates a reaction that edits, or cuts, the DNA for the fluorescent protein. If the DNA is cut, the system does not glow. If the DNA is not cut, the fluorescent protein is made, and the system glows fluorescent.

“We have linked this abstract, really advanced biological concept to the presence or absence of a fluorescent protein,” Stark said. “It’s something students can see, something they can visually understand.”

The curriculum also includes activities that challenge students to consider the ethical questions and dilemmas surrounding the use of gene-editing technologies.

“There is a lot of excitement about being able to edit genomes with these technologies,” Jewett said. “BioBits Health calls attention to a lot of important questions — not only about how CRISPR technology works but about ethics that society should be thinking about. We hope that this promotes a conversation and dialogue about such technologies.”

Reducing resistance

Jewett and Stark are both troubled by a prediction that, by the year 2050, drug-resistant bacterial infections could outpace cancer as a leading cause of death. This motivated them to help educate the future generation of scientists about how antibiotic resistance emerges and inspire them to take actions that could help limit the emergence of resistant bacteria.
In this module, students run two sets of reactions to produce a glowing fluorescent protein — one set with an antibiotic resistance gene and one set without. Students then add antibiotics. If the experiment glows, the fluorescent protein has been made, and the reaction has become resistant to antibiotics. If the experiment does not glow, then the antibiotic has worked.

“Because we’re using cell-free systems rather than organisms, we can demonstrate drug resistance in a way that doesn’t create drug-resistant bacteria,” Stark explained. “We can demonstrate these concepts without the risks.”

A supporting curriculum piece challenges students to brainstorm and research strategies for slowing the rate of emerging antibiotic resistant strains.

Part of something cool

After BioBits was launched in summer 2018, 330 schools from around the globe requested prototype kits for their science labs. The research team, which includes members from Northwestern and MIT, has received encouraging feedback from teachers, students and parents.

“The students felt like scientists and doctors by touching and using the laboratory materials provided during the demo,” one teacher said. “Even the students who didn’t seem engaged were secretly paying attention and wanted to take their turn pipetting. They knew they were part of something really cool, so we were able to connect with them in a way that was new to them.”

“My favorite part was using the equipment,” a student said. “It was a fun activity that immerses you into what top scientists are currently doing.”


The study, “BioBits Health: Classroom activities exploring engineering, biology and human health with fluorescent readouts,” was supported by the Army Research Office (award number W911NF-16-1-0372), the National Science Foundation (grant numbers MCB-1413563 and MCB-1716766), the Air Force Research Laboratory Center of Excellence (grant number FA8650-15-2-5518), the Defense Threat Reduction Agency (grant number HDTRA1-15-10052/P00001), the Department of Energy (grant number DE-SC0018249), the Human Frontiers Science Program (grant number RGP0015/2017), the David and Lucile Packard Foundation, the Office of Energy Efficiency and Renewable Energy (grant number DE-EE008343) and the Camille Dreyfus Teacher-Scholar Program. [emphases mine]

This is an image you’ll find in the abstract for the 2019 paper,

[downloaded from https://pubs.acs.org/doi/10.1021/acssynbio.8b00381]

Here are links and citations for the 2018 papers and the 2019 paper,

BioBits™ Explorer: A modular synthetic biology education kit by Ally Huang, Peter Q. Nguyen, Jessica C. Stark, Melissa K. Takahashi, Nina Donghia, Tom Ferrante, Aaron J. Dy, Karen J. Hsu, Rachel S. Dubner, Keith Pardee, Michael C. Jewett, and James J. Collins. Science Advances 01 Aug 2018: Vol. 4, no. 8, eaat5105 DOI: 10.1126/sciadv.aat5105

BioBits™ Bright: A fluorescent synthetic biology education kit by Jessica C. Stark, Ally Huang, Peter Q. Nguyen, Rachel S. Dubner, Karen J. Hsu, Thomas C. Ferrante, Mary Anderson, Ada Kanapskyte, Quinn Mucha, Jessica S. Packett, Palak Patel, Richa Patel, Deema Qaq, Tyler Zondor, Julie Burke, Thomas Martinez, Ashlee Miller-Berry, Aparna Puppala, Kara Reichert, Miriam Schmid, Lance Brand, Lander R. Hill, Jemima F. Chellaswamy, Nuhie Faheem, Suzanne Fetherling, Elissa Gong, Eddie Marie Gonzalzles, Teresa Granito, Jenna Koritsaris, Binh Nguyen, Sujud Ottman, Christina Palffy, Angela Patel, Sheila Skweres, Adriane Slaton, TaRhonda Woods, Nina Donghia, Keith Pardee, James J. Collins, and Michael C. Jewett. Science Advances 01 Aug 2018: Vol. 4, no. 8, eaat5107 DOI: 10.1126/sciadv.aat5107

BioBits Health: Classroom Activities Exploring Engineering, Biology, and Human Health with Fluorescent Readouts by Jessica C. Stark, Ally Huang, Karen J. Hsu, Rachel S. Dubner, Jason Forbrook, Suzanne Marshalla, Faith Rodriguez, Mechelle Washington, Grant A. Rybnicky, Peter Q. Nguyen, Brenna Hasselbacher, Ramah Jabri, Rijha Kamran, Veronica Koralewski, Will Wightkin, Thomas Martinez, and Michael C. Jewett. ACS Synth. Biol., Article ASAP
DOI: 10.1021/acssynbio.8b00381 Publication Date (Web): March 29, 2019

Copyright © 2019 American Chemical Society

Both of the 2018 papers appear to be open access while the 2019 paper is behind a paywall.

Should you be interested in acquiring a BioBits kit, you can check out the BioBits website. As for ‘conguering’ CRISPR, do we really need to look at it that way? Maybe a more humble appraoch could work just as well or even better, eh?

*’is’ removed from sentence on May 9, 2019.

I hear the proteins singing

Points to anyone who recognized the paraphrasing of the title for the well-loved, Canadian movie, “I heard the mermaids singing.” In this case, it’s all about protein folding and data sonification (from an Oct. 20, 2016 news item on phys.org),

Transforming data about the structure of proteins into melodies gives scientists a completely new way of analyzing the molecules that could reveal new insights into how they work – by listening to them. A new study published in the journal Heliyon shows how musical sounds can help scientists analyze data using their ears instead of their eyes.

The researchers, from the University of Tampere in Finland, Eastern Washington University in the US and the Francis Crick Institute in the UK, believe their technique could help scientists identify anomalies in proteins more easily.

An Oct. 20, 2016 Elsevier Publishing press release on EurekAlert, which originated the news item, expands on the theme,

“We are confident that people will eventually listen to data and draw important information from the experiences,” commented Dr. Jonathan Middleton, a composer and music scholar who is based at Eastern Washington University and in residence at the University of Tampere. “The ears might detect more than the eyes, and if the ears are doing some of the work, then the eyes will be free to look at other things.”

Proteins are molecules found in living things that have many different functions. Scientists usually study them visually and using data; with modern microscopy it is possible to directly see the structure of some proteins.

Using a technique called sonification, the researchers can now transform data about proteins into musical sounds, or melodies. They wanted to use this approach to ask three related questions: what can protein data sound like? Are there analytical benefits? And can we hear particular elements or anomalies in the data?

They found that a large proportion of people can recognize links between the melodies and more traditional visuals like models, graphs and tables; it seems hearing these visuals is easier than they expected. The melodies are also pleasant to listen to, encouraging scientists to listen to them more than once and therefore repeatedly analyze the proteins.

The sonifications are created using a combination of Dr. Middleton’s composing skills and algorithms, so that others can use a similar process with their own proteins. The multidisciplinary approach – combining bioinformatics and music informatics – provides a completely new perspective on a complex problem in biology.

“Protein fold assignment is a notoriously tricky area of research in molecular biology,” said Dr. Robert Bywater from the Francis Crick Institute. “One not only needs to identify the fold type but to look for clues as to its many functions. It is not a simple matter to unravel these overlapping messages. Music is seen as an aid towards achieving this unraveling.”

The researchers say their molecular melodies can be used almost immediately in teaching protein science, and after some practice, scientists will be able to use them to discriminate between different protein structures and spot irregularities like mutations.

Proteins are the first stop, but our knowledge of other molecules could also benefit from sonification; one day we may be able to listen to our genomes, and perhaps use this to understand the role of junk DNA [emphasis mine].

About 97% of our DNA (deoxyribonucleic acid) has been known for some decades as ‘junk DNA’. In roughly 2012, that was notion was challenged as Stephen S. Hall wrote in an Oct. 1, 2012 article (Hidden Treasures in Junk DNA; What was once known as junk DNA turns out to hold hidden treasures, says computational biologist Ewan Birney) for Scientific American.

Getting back to  2016, here’s a link to and a citation for ‘protein singing’,

Melody discrimination and protein fold classification by  Robert P. Bywater, Jonathan N. Middleton. Heliyon 20 Oct 2016, Volume 2, Issue 10 DOI: 10.1016/j.heliyon.2016.e0017

This paper is open access.

Here’s what the proteins sound like,

Supplementary Audio 3 for file for Supplementary Figure 2 1r75 OHEL sonification full score. [downloaded from the previously cited Heliyon paper]

Joanna Klein has written an Oct. 21, 2016 article for the New York Times providing a slightly different take on this research (Note: Links have been removed),

“It’s used for the concert hall. It’s used for sports. It’s used for worship. Why can’t we use it for our data?” said Jonathan Middleton, the composer at Eastern Washington University and the University of Tampere in Finland who worked with Dr. Bywater.

Proteins have been around for billions of years, but humans still haven’t come up with a good way to visualize them. Right now scientists can shoot a laser at a crystallized protein (which can distort its shape), measure the patterns it spits out and simulate what that protein looks like. These depictions are difficult to sift through and hard to remember.

“There’s no simple equation like e=mc2,” said Dr. Bywater. “You have to do a lot of spade work to predict a protein structure.”

Dr. Bywater had been interested in assigning sounds to proteins since the 1990s. After hearing a song Dr. Middleton had composed called “Redwood Symphony,” which opens with sounds derived from the tree’s DNA, he asked for his help.

Using a process called sonification (which is the same thing used to assign different ringtones to texts, emails or calls on your cellphone) the team took three proteins and turned their folding shapes — a coil, a turn and a strand — into musical melodies. Each shape was represented by a bunch of numbers, and those numbers were converted into a musical code. A combination of musical sounds represented each shape, resulting in a song of simple patterns that changed with the folds of the protein. Later they played those songs to a group of 38 people together with visuals of the proteins, and asked them to identify similarities and differences between them. The two were surprised that people didn’t really need the visuals to detect changes in the proteins.

Plus, I have more about data sonification in a Feb. 7, 2014 posting regarding a duet based on data from Voyager 1 & 2 spacecraft.

Finally, I hope my next Steep project will include  sonification of data on gold nanoparticles. I will keep you posted on any developments.

What’s a science historian doing in the field of synthetic biology?

Dominic Berry’s essay on why he, a science historian, is involved in a synthetic biology project takes some interesting twists and turns, from a Sept. 2, 2016 news item on phys.org,

What are synthetic biologists doing to plants, and what are plants doing to synthetic biology? This question frames a series of laboratory observations that I am pursuing across the UK as part of the Engineering Life project, which is dedicated to exploring what it might mean to engineer biology. I contribute to the project through a focus on plant scientists and my training in the history and philosophy of science. For plant scientists the engineering of biology can take many forms not all of which are captured by the category ‘synthetic biology’. Scientists that aim to create modified organisms are more inclined to refer to themselves as the latter, while other plant scientists will emphasise an integration of biological work with methods or techniques from engineering without adopting the identity of synthetic biologist. Accordingly, different legacies in the biosciences (from molecular biology to biomimetics) can be drawn upon depending on the features of the project at hand. These category and naming problems are all part of a larger set of questions that social and natural scientists continue to explore together. For the purposes of this post the distinctions between synthetic biology and the broader engineering of biology do not matter greatly, so I will simply refer to synthetic biology throughout.

Berry’s piece was originally posted Sept. 1, 2016 by Stephen Burgess on the PLOS (Public Library of Science) Synbio (Synthetic Biology blog). In this next bit Berry notes briefly why science historians and scientists might find interaction and collaboration fruitful (Note: Links have been removed),

It might seem strange that a historian is focused so closely on the present. However, I am not alone, and one recent author has picked out projects that suggest it is becoming a trend. This is only of interest for readers of the PLOS Synbio blog because it flags up that there are historians of science available for collaboration (hello!), and plenty of historical scholarship to draw upon to see your work in a new light, or rediscover forgotten research programs, or reconsider current practices, precisely as a recent Nature editorial emphasised for all sciences.

The May 17, 2016 Nature editorial ‘Second Thoughts’, mentioned in Berry’s piece, opens provocatively and continues in that vein (Note: A link has been removed),

The thought experiment has a noble place in research, but some thoughts are deemed more noble than others. Darwin and Einstein could let their minds wander and imagine the consequences of certain actions or natural laws. But scientists and historians who try to estimate what might have happened if, say, Darwin had fallen off the Beagle and drowned, are often accused of playing parlour games.

What if Darwin had toppled overboard before he joined the evolutionary dots? That discussion seems useful, because it raises interesting questions about the state of knowledge, then and now, and how it is communicated and portrayed. In his 2013 book Darwin Deleted — in which the young Charles is, indeed, lost in a storm — the historian Peter Bowler argued that the theory of evolution would have emerged just so, but with the pieces perhaps placed in a different order, and therefore less antagonistic to religious society.

In this week’s World View, another historian offers an alternative pathway for science: what if the ideas of Gregor Mendel on the inheritance of traits had been challenged more robustly and more successfully by a rival interpretation by the scientist W. F. R. Weldon? Gregory Radick argues that a twentieth-century genetics driven more by Weldon’s emphasis on environmental context would have weakened the dominance of the current misleading impression that nature always trumps nurture.

Here is Berry on the importance of questions,

The historian can ask: What traditions and legacies are these practitioners either building on or reacting against? How do these ideas cohere (or remain incoherent) for individuals and laboratories? Is a new way of understanding and investigating biology being created, and if so, where can we find evidence of it? Have biologists become increasingly concerned with controlling biological phenomena rather than understanding them? How does the desire to integrate engineering with biology sit within the long history of the establishment of biological science over the course of the 19th and 20th centuries?

Berry is an academic and his piece reflects an academic writing style with its complicated sentence structures and muted conclusions. If you have the patience, it is a good read on a topic that isn’t discussed all that often.

Replicating brain’s neural networks with 3D nanoprinting

An announcement about European Union funding for a project to reproduce neural networks by 3D nanoprinting can be found in a June 10, 2016 news item on Nanowerk,

The MESO-BRAIN consortium has received a prestigious award of €3.3million in funding from the European Commission as part of its Future and Emerging Technology (FET) scheme. The project aims to develop three-dimensional (3D) human neural networks with specific biological architecture, and the inherent ability to interrogate the network’s brain-like activity both electrophysiologically and optically. It is expected that the MESO-BRAIN will facilitate a better understanding of human disease progression, neuronal growth and enable the development of large-scale human cell-based assays to test the modulatory effects of pharmacological and toxicological compounds on neural network activity. The use of more physiologically relevant human models will increase drug screening efficiency and reduce the need for animal testing.

A June 9, 2016 Institute of Photonic Sciences (ICFO) press release (also on EurekAlert), which originated the news item, provides more detail,

About the MESO-BRAIN project

The MESO-BRAIN project’s cornerstone will use human induced pluripotent stem cells (iPSCs) that have been differentiated into neurons upon a defined and reproducible 3D scaffold to support the development of human neural networks that emulate brain activity. The structure will be based on a brain cortical module and will be unique in that it will be designed and produced using nanoscale 3D-laser-printed structures incorporating nano-electrodes to enable downstream electrophysiological analysis of neural network function. Optical analysis will be conducted using cutting-edge light sheet-based, fast volumetric imaging technology to enable cellular resolution throughout the 3D network. The MESO-BRAIN project will allow for a comprehensive and detailed investigation of neural network development in health and disease.

Prof Edik Rafailov, Head of the MESO-BRAIN project (Aston University) said: “What we’re proposing to achieve with this project has, until recently, been the stuff of science fiction. Being able to extract and replicate neural networks from the brain through 3D nanoprinting promises to change this. The MESO-BRAIN project has the potential to revolutionise the way we are able to understand the onset and development of disease and discover treatments for those with dementia or brain injuries. We cannot wait to get started!”

The MESO-BRAIN project will launch in September 2016 and research will be conducted over three years.

About the MESO-BRAIN consortium

Each of the consortium partners have been chosen for the highly specific skills & knowledge that they bring to this project. These include technologies and expertise in stem cells, photonics, physics, 3D nanoprinting, electrophysiology, molecular biology, imaging and commercialisation.

Aston University (UK) Aston Institute of Photonic Technologies (School of Engineering and Applied Science) is one of the largest photonic groups in UK and an internationally recognised research centre in the fields of lasers, fibre-optics, high-speed optical communications, nonlinear and biomedical photonics. The Cell & Tissue Biomedical Research Group (Aston Research Centre for Healthy Ageing) combines collective expertise in genetic manipulation, tissue engineering and neuronal modelling with the electrophysiological and optical analysis of human iPSC-derived neural networks. Axol Bioscience Ltd. (UK) was founded to fulfil the unmet demand for high quality, clinically relevant human iPSC-derived cells for use in biomedical research and drug discovery. The Laser Zentrum Hannover (Germany) is a leading research organisation in the fields of laser development, material processing, laser medicine, and laser-based nanotechnologies. The Neurophysics Group (Physics Department) at University of Barcelona (Spain) are experts in combing experiments with theoretical and computational modelling to infer functional connectivity in neuronal circuits. The Institute of Photonic Sciences (ICFO) (Spain) is a world-leading research centre in photonics with expertise in several microscopy techniques including light sheet imaging. KITE Innovation (UK) helps to bridge the gap between the academic and business sectors in supporting collaboration, enterprise, and knowledge-based business development.

For anyone curious about the FET funding scheme, there’s this from the press release,

Horizon 2020 aims to ensure Europe produces world-class science by removing barriers to innovation through funding programmes such as the FET. The FET (Open) funds forward-looking collaborations between advanced multidisciplinary science and cutting-edge engineering for radically new future technologies. The published success rate is below 1.4%, making it amongst the toughest in the Horizon 2020 suite of funding schemes. The MESO-BRAIN proposal scored a perfect 5/5.

You can find out more about the MESO-BRAIN project on its ICFO webpage.

They don’t say anything about it but I can’t help wondering if the scientists aren’t also considering the possibility of creating an artificial brain.

Evelyn Fox Keller’s address: “Paradigm Shifts And Revolutions in Contemporary Biology” being livestreamed on Oct. 30, 2012 at 3 pm PDT

Mentioned in my Oct. 3, 2012 posting (mortifyingly, I listed the wrong date in the headline), Evelyn Fox Keller’s talk is accessible to anyone who has an internet connection. Before giving you details about where to go for a link, here’s more about the talk and about Keller,

Fifty years ago, Thomas Kuhn irrevocably transformed our thinking about the sciences with the publication of The Structure of Scientific Revolutions. For all his success, debate about the adequacy and applicability of his formulation persists to this day. Are there scientific revolutions in biology? Molecular genetics, for example, is currently undergoing a major transformation in its understanding of what genes are and of what role they play in an organism’s development and evolution. Is this a revolution? More specifically, is this a revolution of the sort that Kuhn had in mind? How is language used? What implications can we draw from this?

Dr. Keller is the recipient of the prestigious MacArthur ‘Genius’ Award and author of many influential works on science, society and modern biology such as: A Feeling for the Organism: The Life and Work of Barbara McClintock (1983), Reflections on Gender and Science (1985), Secrets of Life, Secrets of Death: Essays on Language, Gender, and Science (1992), The Century of the Gene (2000), Making Sense of Life: Explaining Biological Development with Models, Metaphors and Machines (2002) and The Mirage of a Space Between Nature and Nurture (2010).

You can go here tomorrow (Oct. 30, 2012) to watch Dr. Keller at 3 pm PDT. She is being hosted by,

The Situating Science Strategic Knowledge Cluster, funded by the Social Sciences and Humanities Research Council of Canada, and its partners are pleased to announce Dr. Evelyn Fox Keller as the Situating Science Visiting Scholar in Halifax Oct. 15th-Nov.7th. During her stay, Dr. Keller will participate in a series of public events (below), including a special public evening lecture on Tuesday, Oct. 30th.

Situating Science Strategic Knowledge Cluster; Evolution Studies Group (funded with assistance from Canadian Institute for Advanced Research, CIFAR); Canadian Institutes of Health Research Institute of Genetics Community Support Program, Dalhousie University Department of Biology, Department of Philosophy and Health Law Institute; University of King’s College President’s Office, History of Science and Technology Programme, Contemporary Studies Programme, and Centre for Interdisciplinary Research; Nova Scotia Institute of Science; Saint Mary’s University Department of Philosophy and Faculty of Science;  Mount Saint-Vincent NSERC Atlantic Chair for Women in Science and Engineering, Dean of Arts, and Science and Institute for Women, Gender and Social Justice.

Folding, origami, and shapeshifting and an article with over 50,000 authors

I’m on a metaphor kick these days so here goes, origami (Japanese paper folding), and shapeshifting are metaphors used to describe a certain biological process that nanoscientists from fields not necessarily associated with biology find fascinating, protein folding.


Take for example a research team at the California Institute of Technology (Caltech) working to exploit the electronic properties of carbon nanotubes (mentioned in a Nov. 9, 2010 news item on Nanowerk). One of the big issues is that since all of the tubes in a sample are made of carbon getting one tube to react on its own without activating the others is quite challenging when you’re trying to create nanoelectronic circuits. The research team decided to use a technique developed in a bioengineering lab (from the news item),

DNA origami is a type of self-assembled structure made from DNA that can be programmed to form nearly limitless shapes and patterns (such as smiley faces or maps of the Western Hemisphere or even electrical diagrams). Exploiting the sequence-recognition properties of DNA base paring, DNA origami are created from a long single strand of viral DNA and a mixture of different short synthetic DNA strands that bind to and “staple” the viral DNA into the desired shape, typically about 100 nanometers (nm) on a side.

Single-wall carbon nanotubes are molecular tubes composed of rolled-up hexagonal mesh of carbon atoms. With diameters measuring less than 2 nm and yet with lengths of many microns, they have a reputation as some of the strongest, most heat-conductive, and most electronically interesting materials that are known. For years, researchers have been trying to harness their unique properties in nanoscale devices, but precisely arranging them into desirable geometric patterns has been a major stumbling block.

… To integrate the carbon nanotubes into this system, the scientists colored some of those pixels anti-red, and others anti-blue, effectively marking the positions where they wanted the color-matched nanotubes to stick. They then designed the origami so that the red-labeled nanotubes would cross perpendicular to the blue nanotubes, making what is known as a field-effect transistor (FET), one of the most basic devices for building semiconductor circuits.

Although their process is conceptually simple, the researchers had to work out many kinks, such as separating the bundles of carbon nanotubes into individual molecules and attaching the single-stranded DNA; finding the right protection for these DNA strands so they remained able to recognize their partners on the origami; and finding the right chemical conditions for self-assembly.

After about a year, the team had successfully placed crossed nanotubes on the origami; they were able to see the crossing via atomic force microscopy. These systems were removed from solution and placed on a surface, after which leads were attached to measure the device’s electrical properties. When the team’s simple device was wired up to electrodes, it indeed behaved like a field-effect transistor


For another more recent example (from an August 5, 2010 article on physorg.com by Larry Hardesty,  Shape-shifting robots),

By combining origami and electrical engineering, researchers at MIT and Harvard are working to develop the ultimate reconfigurable robot — one that can turn into absolutely anything. The researchers have developed algorithms that, given a three-dimensional shape, can determine how to reproduce it by folding a sheet of semi-rigid material with a distinctive pattern of flexible creases. To test out their theories, they built a prototype that can automatically assume the shape of either an origami boat or a paper airplane when it receives different electrical signals. The researchers reported their results in the July 13 issue of the Proceedings of the National Academy of Sciences.

As director of the Distributed Robotics Laboratory at the Computer Science and Artificial Intelligence Laboratory (CSAIL), Professor Daniela Rus researches systems of robots that can work together to tackle complicated tasks. One of the big research areas in distributed robotics is what’s called “programmable matter,” the idea that small, uniform robots could snap together like intelligent Legos to create larger, more versatile robots.

Here’s a video from this site at MIT (Massachusetts Institute of Technology) describing the process,

Folding and over 50, 000 authors

With all this I’ve been leading up to a fascinating project, a game called Foldit, that a team from the University of Washington has published results from in the journal Nature (Predicting protein structures with a multiplayer online game), Aug. 5, 2010.

With over 50,000 authors, this study is a really good example of citizen science (discussed in my May 14, 2010 posting and elsewhere here) and how to use games to solve science problems while exploiting a fascination with folding and origami. From the Aug. 5, 2010 news item on Nanowerk,

The game, Foldit, turns one of the hardest problems in molecular biology into a game a bit reminiscent of Tetris. Thousands of people have now played a game that asks them to fold a protein rather than stack colored blocks or rescue a princess.

Scientists know the pieces that make up a protein but cannot predict how those parts fit together into a 3-D structure. And since proteins act like locks and keys, the structure is crucial.

At any moment, thousands of computers are working away at calculating how physical forces would cause a protein to fold. But no computer in the world is big enough, and computers may not take the smartest approach. So the UW team tried to make it into a game that people could play and compete. Foldit turns protein-folding into a game and awards points based on the internal energy of the 3-D protein structure, dictated by the laws of physics.

Tens of thousands of players have taken the challenge. The author list for the paper includes an acknowledgment of more than 57,000 Foldit players, which may be unprecedented on a scientific publication.

“It’s a new kind of collective intelligence, as opposed to individual intelligence, that we want to study,”Popoviç [principal investigator Zoran Popoviç, a UW associate professor of computer science and engineering] said. “We’re opening eyes in terms of how people think about human intelligence and group intelligence, and what the possibilities are when you get huge numbers of people together to solve a very hard problem.”

There’s a more at Nanowerk including a video about the gamers and the scientists. I think most of us take folding for granted and yet it stimulates all kinds of research and ideas.

Science festivals in the US; nanoparticles and environmental health and safety report from ENRHES; new technique in molecular biology; PEN’s site remediation webcast commentary

I just came across a notice for the first ever USA Science and Engineering Festival to be held in Washington, DC, Oct. 10-24, 2010. From the Azonano news item,

Agilent Technologies Inc. (NYSE:A) today announced its support of the USA Science & Engineering Festival, the country’s first national science festival. The event will take place in Washington, D.C., in October 2010. The festival, expected to be a multi-cultural and multi-disciplinary celebration of science in the United States, will offer science and engineering organizations throughout the country the opportunity to present hands-on science activities to inspire the next generation of scientists and engineers. Festival organizers already have engaged more than 350 participants from the nation’s leading science and engineering organizations.

From what I’ve seen of their website, they are using the term multi-disciplinary in a fairly conservative sense, i. e., different science and engineering disciplines are being brought together. This contrasts with the approach used in the World Science Festival, being held in New York, June 2-6, 2010, where they mash together artists as well as scientists from many different disciplines.

Michael Berger at Nanowerk sputters a bit as he comments on the Engineered Nanoparticles Review of Health and Environmental Safety (ENRHES) report,

Before we take a look at the report’s findings, it’s quite remarkable that the authors feel compelled to start their introduction section with this sentence: “Nanotechnology is a sector of the material manufacturing industry that has already created a multibillion $US market, and is widely expected to grow to 1 trillion $US by 2015.” Firstly, a lot of people would argue with the narrow definition of nanotechnology as being a sector of the material manufacturing industry. Secondly, it appears that still no publicly funded report can afford to omit the meaningless and nonsensical reference to a ‘trillion dollar industry by 2015’. It really is astonishing how this claim gets regurgitated over and over again – even by serious scientists – without getting scrutinized (read “Debunking the trillion dollar nanotechnology market size hype”). It would be interesting to know if scientific authors, who otherwise operate in a fact-based world, just accept a number picked out of thin air by some consultants because it helps impress their funders; or if they deliberately use what they know is a fishy number because the politicians and bureaucrats who control the purses are easily fooled by sensational claims like these and keep the funding coming.

Sadly, picking a number out of thin air happens more often than we like to believe. A few years back I was reading a book about food and how it’s changing as we keep manipulating our food products to make them last longer on the shelf, etc. In one chapter of the book, the author chatted with an individual who helped to define high cholesterol. As he told the story, he and his colleagues (scientists all) got in a room and picked a number that was used to define a high cholesterol count. (I will try to find the title of that book, unfortunately the memory escapes me at the moment. ETA: Mar.4.10, the book is by Gina Mellet, Last chance to eat, 2004) I’ve heard variations of this business of picking a number that sounds good before.

As for the rest of the ENRHES report, Berger has this to say,

Thankfully, the rest of the report stands on solid ground.

I’m using those last two words, “solid ground” to eventually ease my way into a discussion about site remediation and the Project on Emerging Nanotechnologies’ (PEN) recent webcast. First, there’s a brief and related item on molecular biology.

Scientists at the University of Chicago are trying to develop a method for understanding how biological processes emerge from molecular interactions. From the news item (which includes an audio file of Andre Dinner, one of the scientists, discussing his work) on physorg.com,

Funded by a $1 million grant from the W.M. Keck Foundation, University of Chicago scientists are aiming to develop a reliable method for determining how biological processes emerge from molecular interactions. The method may permit them to “rewire” the regulatory circuitry of insulin-secreting pancreatic beta cells, which play a major role in type-2 diabetes.

A second goal: to control cell behavior and function more generally, which may ultimately culminate in other applications, including the bioremediation of environmental problems.

The four scientists [Aaron Dinner, Louis Philipson, Rustem Ismagilov, and Norbert Scherer] share an interest in the collective behavior of cells that emerges from a complex ensemble of atoms and molecules working in concert at different scales of time and space. “In a living system you have this hierarchy of coupled time and length scales,” Dinner said. “How is it that all of these different dynamics at one time and length scale get coupled to dynamics at another scale?”

In other words, how does life begin? I know that’s not the question they’re asking but this work has to lead in that direction and I imagine the synthetic biology people are watching with much interest.

In the more immediate future, this work in molecular biology may lead to better bioremediation, which was the topic at hand on the Project on Emerging Nanotechnologies’ recent (Feb.4.10) webcast.From their website (you can click to view the webcast [approx. 54 mins.] from here),

A new review article appearing in Environmental Health Perspectives (EHP) co-authored by Dr. Todd Kuiken, research associate for the Project on Emerging Nanotechnologies (PEN), Dr. Barbara Karn, Office of Research and Development, U.S. Environmental Protection Agency and Marti Otto, Office of Superfund Remediation and Technology Innovation, U.S. Environmental Protection Agency focuses on the use of nanomaterials for environmental cleanup. It provides an overview of current practices; research findings; societal issues; potential environment, health, and safety implications; and possible future directions for nanoremediation. The authors conclude that the technology could be an effective and economically viable alternative for some current site cleanup practices, but potential risks remain poorly understood.

There is an interactive map of remediation sites available here and, if you scroll down to the bottom of the page, you’ll find a link to the review article or you can go here.

I found the information interesting although I was not the intended audience. This was focused primarily on people who are involved in site remediation and/or are from the US. The short story is that more research needs to be done and there have been some very promising results. The use of nanoscale zero-valent iron (nZVI) nanoparticles was the main topic of discussion. It allows for ‘in situ’ site remediation, in other words, you don’t need to move soil and/or pump water through some treatment process. It’s not appropriate for all sites. It can be faster than the current site remediation treatments and it’s cheaper. There was no mention of any problems or hazards using nZVI but there hasn’t been much research either. The technique is now being used in seven different countries (including Canada with one in Ontario and one in Quebec). If I understand it rightly, there is no requirement to report nanotechnology-enabled site remediation so these numbers are based on self-reports. From the article in Environment Health Perspectives,

The number of actual applications of nZVI is increasing rapidly. Only a fraction of the projects has been reported, and new projects show up regularly. Figure 2 and Supplemental Material, Table 2 (doi:10.1289/ehp.0900793.S1) describe 44 sites where nanoremediation methods have been tested for site remediation.

I think that’s it for today, tomorrow some news from NISENet (Nanoscale Informal Science Education Network).