Designing synthetic DNA nanoparticles that assemble into tubules

How does nature assemble nanoscale structures? Unlike the typical top-down methods for manufacturing, biological systems manufacture functional nanomaterials from the bottom up using a process called self-assembly. In self-assembly, individual ‘building blocks’ are encoded with instructions about how to interact with one another. As a result, ordered structures spontaneously form from a soup of building blocks through thermal fluctuations alone. Famous examples of self-assembling structures in nature include viral capsids, which protect the genetic material and orchestrate viral infections, and microtubules, which form part of the highway systems used for intracellular transportation. However, until recently, manufacturing similarly complex nanostructures from synthetic materials was out of reach because there were no methods for synthesizing building blocks with the kinds of complex geometries and interactions common to biological molecules.

In collaboration with the Dietz Lab at the Technical University of Munich and the Grason Group at the University of Massachusetts Amherst, a team of scientists from the Rogers Lab, Hagan Group,  and Fraden Lab in the Department of Physics at Brandeis developed a class of nanoscale particles that can overcome this hurdle. They designed and synthesized triangular building blocks using a technique known as DNA origami, in which the single-stranded DNA genome from a bacteriophage is ‘folded’ into a user-prescribed 3D shape using a cocktail of short DNA oligonucleotides. The triangular particles that they designed bind to other triangles through specific edge-edge interactions with bond angles that can be independently tuned to make a surface with programmable curvature.

Daichi Hayakawa, a Ph.D. student in the Rogers Lab, tuned the triangle design so that the particles would spontaneously assemble into a tubule with a programmed width and chirality. Interestingly, the assembled tubules were highly polymorphic. In other words, the width and chirality varied from tubule to tubule. Working together with the Hagan Group in Physics, the team rationalized this observation by considering the ‘softness’ of the edge interaction, which allows thermal fluctuations to steer assembly away from the target geometry. To constrain this polymorphism, the research team came up with an alternative method. By using more than one distinct triangle type to assemble a single tubule geometry, they found that they could eliminate some of these off-target structures, thereby making tubule assembly more specific.

In summary, this work highlights two avenues for increasing the fidelity of self-closing structures self-assembled from simple building blocks: control of the curvature through precise geometrical design and addressable complexity through increasing the number of unique species in the assembly mixture. Not only will this result be useful for constructing self-closing nanostructures through self-assembly, but it may also help us understand the role of symmetry and complexity in other self-closing structures found in nature.

Publication:

Geometrically programmed self-limited assembly of tubules using DNA origami colloids. Daichi Hayakawa, Thomas E. Videbaek, Douglas M. Hall and W. Benjamin Rogers.  Proc Natl Acad Sci USA. 2022 Oct 25;119(43):e2207902119.

Breaking the barriers to manufacture thermoplastic microfluidics!

Thermoplastics, such as Cyclin Olefin Copolymer, are used in commercial applications of microfluidics because they are biocompatible, have good material properties such as optical clarity, low fluorescence, high toughness and are cheap to mass produce. However, there are challenges for academic labs to make thermoplastic microfluidics devices. Fabricating molds for thermoplastics is expensive and other process steps, such as sealing the chip and interfacing the chip to the lab are difficult. In a recent publication, the Fraden lab described an inexpensive method for rapid prototyping of thermoplastic microfluidics suitable for academic labs for applications such as x-ray diffraction of protein crystals produced on the same chip in which they were crystallized, or for labs seeking to manufacture a thermoplastic prototype of a microfluidic device in order to demonstrate the potential for mass production. This process will facilitate the transfer of University developed microfluidics to commercialization.

Rapid prototyping of cyclic olefin copolymer (COC) microfluidic devices. S. Ali Aghvami, Achini Opathalage, Z.K. Zhang, Markus Ludwig, Michael Heymann, Michael Norton, Niya Wilkins, Seth Fraden. Sensors and Actuators B: Chemical. Volume 247, August 2017, Pages 940-949.

 

REU Students Arrive for 2016 Summer Research

Amber Jones and Susan Okrah

Alongside the more than 100 Brandeis science undergrads doing research this summer, there are 19 students who are participating in our Research Experiences for Undergraduates (REU) programs. Some students are from Brandeis, but most call universities in Kansas, Virginia, Pennsylvania, New Jersey their academic homes. Eight students are from Hampton University as part of the Partnership for Research and Education in Materials (PREM) initiative between Hampton and Brandeis. The two universities are focused on fostering interest in research science in under-represented groups of undergraduates.

The two independent REU programs were each created 6 years ago with funding from the National Science Foundation (NSF) with a goal of providing a 10-week period of intensive lab research experience to rising sophomores and juniors interested in scientific careers. Professor Susan Lovett is the director of the Cell and Molecular Visualization REU and Dr. Anique Olivier-Mason is the director of the Material Research Science and Engineering Center (MRSEC) REU.

The online application process required each student to submit a transcript, two letters of recommendation and write two essays describing their research experience (if any) and their academic and research goals. This year, 8 students are participating in the MRSEC site; 11 students are working in the Biology-based Cell and Molecular Visualization REU.

Amber Jones, who is going to be a junior at Hampton University this fall, is working in the Avi Rodal lab where she is researching how proteins can be taken on and off of cell membranes. From here, she is hoping to target specific proteins that will ultimately aid in disease research.

Amber has worked in a lab before, but believes nothing could have prepared her for her experience at Brandeis. Her REU lab work has been very involved, but she wasn’t expecting the ups and downs that are a part of lab research. The graduate students and other lab members have been supportive. She has been told “it’s okay; it’s science!”

Returning REU student, Alex Cuadros is working in the Liz Hedstrom lab, says he can go to Cell and Molecular Visualization REU coordinators Cara Pina and Laura Laranjo for assistance. They “have more experience in the lab and they tell me that things don’t always work for them. They say that ‘it’s just part of the science’.”

Nicholas Martinez, who is working in Timothy Street’s lab said, “The biggest challenge I have encountered this summer with my research is being able to do cope with disappointment. Since I am working on a defined timetable and my time here at Brandeis is limited, I want to make as much progress as possible with my research.”

Susan Okrah is working in the Seth Fraden lab this summer. She believes this experience is different from a Chemistry class at Hampton University where you are given an experiment and the results are known. In the REU program, students are given a project that is a subset of their lab’s research. Unlike school, the outcome of their research is unknown. Susan said, “We are given a direction and told to see if it works.”

Alex said that in class he has learned how to do experiments, but at Brandeis he is “doing something that has not been done before so there’s no right method.” It’s also helpful to be able to ask advice about how to approach his research and “Then you go back and you figure out how to do it. You are forced to think independently.”

During the academic year, Alex works in a Biochemistry lab at UMass Amherst. He landed the job last fall as a direct result of his 2015 REU research. How did he get the job in a very competitive environment on the large UMass campus? He presented the poster that he prepared for SciFest 2015.

The most valuable lesson learned this summer? “Resilience” said Amber. Learning to cope with the changing tides of research is important. As Susan said, “people don’t really understand what goes into research until they’re here.”

Part of the REU program involves attending journal clubs and lab meetings, but the most valuable experience of this program is simply being in a lab. Both Amber and Susan agree that anyone thinking about a career in research should go through an intensive research experience such as this. Jones noted, “I wasn’t really expecting to get this type of understanding. I really appreciate that now that I’m here.”

Both Nicholas and Alex ultimately would like to attend graduate school. For Nicholas, “being able to participate in the Cell and Molecular Visualization REU program at Brandeis has been a great opportunity for me to diversify my knowledge and skill set in scientific research prior to applying for graduate school next year. This It has been a great way for me to gain experience in a new area of research that I am interested in and to become part of a different scientific community.”

The REU students are hard at work wrapping up their research and preparing their posters for the SciFest 2016 poster session that is scheduled for Thursday, August 4.

SPROUT Continues Growing Support for Brandeisian Innovators

Program Will Bestow Up to $100,000 to Promising Research Proposals

Could your research impact the world or do you have an idea that could create positive change? Need funding? SPROUT can help with that.

The popular SPROUT program, now in its sixth year, has announced increased funding for the 2016 round of proposals. SPROUT is funded by the Office of the Provost and run by Office of Technology Licensing. This year the Hassenfeld Family Innovation Center, recently created to support entrepreneurial and innovative collaborations happening across campus, contributed an additional $50,000 to be disbursed among the most promising requests.

Historically, the program has supported a diverse scope of lab-based innovations from all departments in the sciences  including Biology, Biochemistry, Physics, and Chemistry.  Past candidates have proposed projects ranging  from early‐stage research and development to patent‐ready projects ranging from treatments for diseases to lab tools.  Brandeis lab scientists have pitched their projects, including HIV vaccines (Sebastian Temme, Krauss lab),  neuroslicers (Yasmin Escobedo Lozoya, Nelson lab) and the use of carrot fiber as an anti-diabetic  (Michelle Landstrom, Hayes lab) to a panel of distinguished, outside judges. A SPROUT award can jumpstart your innovation and lead to continued opportunities. SPROUT awardees researching the use of carrot fiber as an anti-diabetic food agent were just awarded additional funding by the Massachusetts Innovation Commercialization Seed Fund program.

Other successful projects include “Enzymatic Reaction Recruits Chiral Nanoparticles to Inhibit Cancer Cells” led by Xuewen Du from the Xu lab, “Semaphorin4D: a disease‐modifying therapy for epilepsy” led by Daniel Acker of the Paradis lab, “X‐ray transparent Microfluidics for Protein Crystallization” led by Achini  Opathalage from the Fraden lab and “New and Rational Catalyst Development for Green Chemistry”  from the Thomas lab.  Those interested in learning more about past SPROUT winners are invited to read this recent Brandeis NOW article. A list of additional winners, along with their executive summaries, is available on the Brandeis OTL website.

Teams seeking support for scientific projects which require bench research, lab space, and/or lab equipment are encouraged to submit an abstract prior to the March 7 deadline. The competition is open to the entire Brandeis community including faculty, staff, and students. The Office of Technology Licensing will conduct information sessions on Thursday, February 25th 11:30 a.m.‐12:30 p.m. in Volen 201 and on Monday, February 29th 1:00 p.m.‐2:00 p.m. at the Shapiro Science Center, 1st Floor Library. Staff will address the application process as well as specific questions and interested applicants are highly encouraged to attend.

More details regarding the SPROUT awards, process and online application may be found at bit.ly/SPROUT16.

DIY your own Programmable Illumination Microscope

The Fraden Group describes how to build your own Programmable Illumination Microscope in the American Journal of Physics

Have you ever marveled at the equipment used in a research lab? Have you ever wondered how a specialized piece of equipment was made? Have you ever wondered how much it would cost to build your own research microscope? Have you ever considered trying to make your own research microscope? The details on how the Fraden Group builds their Programmable Illumination Microscope for under $4000 was recently published in the American Journal of Physics.

The Programmable Illumination Microscope or PIM is a highly specialized microscope where the illumination for the sample being imaged comes from a modified commercial projector, nearly identical to the ones mounted in every classroom. For the PIM the lens that projects the image onto the screen is removed and replaced with optics (often the same lens in reverse) that shrinks the image down so that it can be focused through the microscope objective onto the sample. The light coming from the projector, which is the illumination source for the microscope, can be modified in realtime based on the image being captured by the camera. Thus the illumination is not only programmable but can also be algorithmic and provide active feedback.

This new publication in the American Journal of Physics, which is published by the American Association of Physics Teachers, is intended to help small teaching and research labs across the country develop their own PIMs to be built and used by undergraduate students. The paper includes schematics and parts lists for the hardware as well as instructions and demonstration code for the software. Any other questions can be directed to the authors Nate Tompkins and Seth Fraden.

Irving Epstein Interviewed by NPR about Alan Turing

Irving Epstein, Professor of Chemistry, was recently interviewed by NPR about Alan Turing and a paper (Testing Turing’s theory of morphogenesis in chemical cells) that he co-authored with Nathan Tompkins, Ning Li, Camille Girabawe, Michael Heymann, Seth Fraden and G. Bard Ermentrout earlier this year. The paper discussed an experiment that they performed that confirmed and improved upon Alan Turing’s theory about morphogenesis.

Alan Turing is credited with inventing the modern computer and breaking the German Enigma code during World War II. That work is spotlighted in the upcoming movie titled “The Imitation Game”. After World War II, Turing turned his focus to biology. He investigated how a single embryonic cell develops into a complex organism with hundreds of different kinds of cells. He wrote The Chemical Basis of Morphogenesis in 1952.

Listen to the interview …

Sprout Grant Winners Announced

Winners of the 2013 Sprout Grant competition held by the Brandeis Office of Technology and Licensing have been announced. Sprout grants support research that is “novel, patentable and [has] commercial potential“, and encourage students to think about new and different ways to apply their basic science for practical good. Each team applying for a grant must be led by a Brandeis student or postdoc (noted in asterisks below), who were responsible for presenting their proposals to the review panel.

Teams that received funding.

• Marcus Long (*), Ann Lawson, Lior Rozhansky ’15, and Liz Hedstrom: $20,000 to develop novel inhibitors of deubiquitinating enzymes;
• Michael Heymann (*), Achini Opathalage, Dongshin Kim, and Seth Fraden: $5,500 for its development of CrystalChip;
• Michael Spellberg (*), Calla Olson, Marissa Donovan, and Mike Marr: $10,000 to develop a tool to purify Calmodulin-tagged recombinant proteins;
• Julian Eskin (*) and Bruce Goode: $2,000 for work on a rapid and efficient kit to purify actin;
• Eugene Goncharov ’13 (*), Yuval Galor ’15,  and Alex Bardasu ’15: $2,500 towards development of their iPhone app LineSaver, which collects data on local hotspots and gives users an estimated wait-time for restaurants, clubs and tourist attractions.

You can read more at BrandeisNOW

Ye Zhang wins Materials Research Society Poster Award

Ye Zhang, a Postdoctoral Fellow from Prof. Bing Xu’s research group at Brandeis, won the 2012 MRS Fall Meeting Poster Awards for her poster titled Self-oscillatory Hydrogels Driven by Belousov-Zhabotinsky Reaction within the symposium on Bioinspired Directional Surfaces-From Nature to Engineered Textured Surfaces & Precision Polymer Materials-Fabricating Functional Assemblies, Surfaces, Interfaces, and Devices. The goal of the project is to make materials that operate like synthetic cardiac or intestinal muscles; feed them and they will pump forever, or as long as the arteries remain open. Ye, the poster’s lead author, is a member of the Brandeis Materials Research Science and Engineering Center (MRSEC) working on project involving the groups of Profs. Bing Xu, Irving Epstein and Seth Fraden of the Chemistry and Physics Departments.

Ye’s work focuses on the development and study of active matter based on non-linear chemical dynamics, specifically the Belousov-Zhabotinsky reaction. Beginning two years ago she systematically modified a class of gels that exhibit periodic volume oscillations which were produced by other groups. First, Ye succeeded in significantly improving the amplitude of volume oscillations. Next, she developed several novel self-oscillatory systems and established a systematic way to improve the bulk material properties of the synthetic heart.  To build a reliable beating heart, Ye optimized the molecules building the material at the molecular level of tens to hundreds of atoms, or scales of 1 nm and then figured out how to assemble them into networks of polymers on the scales of 10 – 100 nm, and then further assembled them on a longer length scale, into elastic networks on the scales of microns, and finally sculpted the resulting rubbery materials using photolithographic and microfluidic methods into useful shapes for study and application. Ye’s award is a recognition of her contribution to molecular engineering and serves as a quintessential example of the  “bottom-up” construction methods exemplified by the interdisciplinary teams of the Brandeis MRSEC.

Memorandum of Understanding between the Brandeis Materials Research Science and Engineering Center (MRSEC) and the Robot Research Initiative (RRI), Chonnam National University, South Korea

 

Dr. Jong-Oh Park (left) and Dr. Seth Fraden pause in front of the MOU banner during the inauguration ceremony.

On August 10, 2012 Dr. Jong-Oh Park and Dr. Sukho Park, Director and Principal Investigator of the Robot Research Initiative (RRI), respectively, visited Brandeis as part of an inauguration ceremony of the Memorandum of Understanding (MOU) between the Brandeis Materials Research Science and Engineering Center (MRSEC) (Director: Seth Fraden, PhD) and the RRI (Director: Jong-Oh Park, Dr.-Ing). The RRI is a world leader in the field of robotics, focusing on microscale engineering applications and surgery, while the Brandeis MRSEC program focusses on biomaterials and active matter. The two institutions have agreed to work together to transform cutting-edge biophysical science into engineering applications for drug delivery.

Collaboration between the two institutions was first established on March 1, 2012, with a three-year subcontract (KRW  120,000,000 / yr) awarded to the MRSEC by the RRI for the development of micro-swimming robots based on synthetic cilia (PI: Dongshin Kim, co-PI: Zvonimir Dogic). Dr. Fraden welcomed the new Memorandum, saying that it would fortify the collaboration efforts of both institutions.

As part of the exchange program laid out by the MOU, Dr. Sukho Park is planning to visit Brandeis in 2013 to spend a year working on the development of micro-actuators based on microtubules and active hydrogels. There are opportunities for the exchange of students between our two universities.