Scientists have drawn up molecular blueprints of a tiny cellular “nanomachine,” whose evolution is an extraordinary feat of nature, by using one of the brightest X-ray sources on Earth.

The scientists produced the structural map of this nanomachine — diacylglycerol kinase — by using a “hit and run” crystallography technique. In doing so, they have been able to understand how the tiny enzyme performs critical cellular duties — answering questions that have been on the table for more than 50 years about this “paradigmatic protein.” This graphic shows the structure of diacylglycerol kinase (DgkA) determined with the Free Electron Laser in Stanford, California. This new structure has been deposited in the protein data bank under the code 4UYO. Download Full Image

Kinases are key players in metabolism, cell signalling, protein regulation, cellular transport, secretory processes, and many other cellular pathways that allow us to function healthily. They coordinate the transfer of energy from certain molecules to specific substrates, affecting their activity, reactivity and ability to bind other molecules.

Diacylglycerol kinase, the focus of this study, plays a role in bacterial cell wall synthesis. It is a small, integral membrane enzyme that coordinates a particularly complex reaction: Its lipid substrate is hydrophobic (repelled by water) and resides in cell membranes, while its co-substrate, ATP, is entirely water soluble. 

How it does this had remained a mystery for decades, but the newly produced blueprints have answered these questions.

“How this diminutive nanomachine, less than 10 nm tall, brings these two disparate substrates together at the membrane interface for reaction is revealed in a molecularly detailed crystal structure. It is the smallest known kinase, and seeing its form with crystal clarity is now helping us to answer questions that formed from over 50 years of work on this paradigmatic protein,” said Martin Caffrey, professor of membrane structural and functional biology at Trinity College Dublin. 

Figuring out how this tiny machine works at the molecular level was enormously facilitated by the use of one of the brightest X-ray sources on Earth, the X-ray free-electron laser at the Stanford Linear Accelerator Center.

Professor Caffrey added: “This instrument produces bursts of X-rays just femtoseconds (a quad-trillionth of a second) long. With these short bursts we were able to obtain structural information about the enzyme before it vaporized through radiation damage in what I tritely refer to as 'hit and run' serial crystallography.”  

According to Petra Fromme, the director of the Center for Applied Structural Discovery at Arizona State University’s Biodesign Institute and a co-author of the current study, “This is the first structure of a protein that is a membrane-integral enzyme and important biocatalyst in the cell.” (Biocatalysts speed up the rate of critical biological reactions.)

The tiny kinase is one of the research targets for the NIH-funded Center for Membrane Proteins in Infectious Diseases at ASU, which is devoted to unraveling the molecular basis of viral and bacterial proteins involved in diseases as well as the human proteins defending the body from pathogen attack.

The ASU team contributed to the work with expertise in crystal growth and sample injection, as well as data collection and evaluation. In the future, the scientists hope to extend their free-electron laser work to make “X-ray movies” of this remarkable nanomachine, so as to watch how it “does chemistry” in atomic detail in real time. The article describing the work has just been published in the leading journal Nature Communications.

The team of researchers at ASU includes faculty Wei Liu, Petra Fromme and Raimund Fromme from the School of Molecular Sciences, and John Spence, Uwe Weierstall and Nadia Zatsepin from the Department of Physics, researcher Ingo Grotjohann as well as graduate students Shibom Basu, Christopher Kupitz and Kimberley Rendek.  

Editor's note: This story is part of a series of student profiles that are part of our December 2015 commencement coverage.

As the end of the fall and spring semesters approach, each of the six Ira A. Fulton Schools of Engineering select one undergraduate student in each of its academic degree programs as its Outstanding Program Graduate. A number of other students are honored as Distinguished Graduates, chosen both by the Fulton Schools as well as the Dean’s Office for their notable accomplishments beyond the classroom. 2015 Outstanding and Distinguished Graduates. Download Full Image

Below are a few of the students that were chosen as this years Outstanding and Distinguished Graduates. View all profiles here.

Outstanding Graduates

These students are among the leading performers in academic studies, with high grade point averages for their classroom work and related research training throughout their undergraduate years.

In addition, they have contributed to the Fulton Schools of Engineering’s mission through their efforts in activities such as research, mentoring, service to others and leadership on student engineering projects and team competitions.

Samantha Janko
BSE in Engineering
Home schooled in Gilbert, Arizona

Samantha Janko started at Chandler Gilbert Community College when she was 14. She participated in FURI for the spring 2015 and fall 2015 semesters. As a part of FURI, she participated in research related to adaptive control of campus cooling systems, with the aim of reducing cooling system costs and energy use on the ASU campuses. She feels her biggest achievement was continuing research with her advisor, Assistant Professor Nathan Johnson, which resulted in presenting at a conference, being lead author on a journal article and a study abroad trip to Aruba

Why did you choose ASU?
I chose to come to ASU for the vast number of opportunities they offer within engineering including research and chances to work with industry partners. Specifically, I chose the Polytechnic School for their hands-on engineering program that would provide me with opportunities to gain real experience in my field.

Tell me about a memorable moment at ASU?  
One of my most memorable moments at ASU was my experience with studying abroad. I traveled to Aruba with a group of students to learn about sustainability in an island setting. The experience opened my eyes to the multidisciplinary characteristics of sustainability, and that becoming green is as much of a socio-economic and cultural issue as it is a technical engineering issue. This travel, along with my research in sustainability with my advisor, inspired me to continue my studies in graduate school with a PhD in systems engineering.

Can you name a professor that was instrumental in helping you grow?
Nathan Johnson was a professor who impacted my education and growth as a student. He has provided me with so many opportunities to grow and learn from research, as well as assisted me in improving my project management and writing abilities. He has introduced me to the real world of engineering research, and is always open to answering questions I have whether it be technical questions or questions about professional development and graduate school.

What are your plans after graduation?
I have plans to continue my education next year as a master’s student in the Engineering M.S. program, followed by work as a PhD candidate in systems engineering.

Kenneth Lozes
BSE in Aerospace Engineering
Graduated from Washington High School in Phoenix, Arizona

Lozes was in the Society of Automotive Engineers (SAE) aircraft design club at ASU that designs, builds and flies a radio-controlled aircraft to compete in the SAE Heavy Lift Competition. He was the composite structures and aerodynamics team lead, and led the wing design and fabrication effort this year for the project, helping to build an eight-foot foot wing prototype that improved on the wing the club built last year. He also worked with the Orbital Sciences company (now Orbital ATK), where he learned about the engineering of space launch vehicles. He was awarded the ASU Provost’s Scholarship and made the Dean’s List every semester.

What led you to choose to study engineering and to decide on the specific major you chose?
I grew up fascinated by the idea of living in space, like in all the science fiction shows I watched, and I always loved going to aerospace museums and air shows, and even reading all technical books about fighter jets that my father would bring home for me. So I think I kind of chose aerospace engineering a long time before I went to college.

What has been most rewarding about your undergraduate years at ASU? What has been most challenging?
The most rewarding experience has been working at the Engineering Tutoring Center, where I am one of lead tutors. I have really enjoyed helping students understand all the fundamental engineering concepts. In addition, the deep understanding of these concepts I have gained over the years has helped tremendously in applying them to my higher-level classes as well as real-world problems.

What are your plans after graduation?
I plan to continue going to school to earn a master’s degree in the 4+1 program, focusing on studying the engineering of propulsion systems for high-speed aerial vehicles and rockets. I would like to be part of making access to outer space much safer and more economical. My dream would be to start a company to develop a propulsion system to do just that.

Sydney Vanda
BSE in Biomedical Engineering and BSE in Computer Systems Engineering
Graduated from Corona del Sol High School in Tempe

Sydney Vanda is a double major in Computer Systems Engineering and Biomedical Engineering and is in Barrett, the Honors College. She holds a Regents High Honors Endorsement, was a three-time recipient of the Kroger Dependent Scholarship, received the 2012 Impact Award for EPICS and has been inducted in the Tau Beta Pi and Eta Kappa Nu Engineering honors societies. She participated in FURI and EPICS. She also sang in the Barrett Choir and was on intramural co-ed basketball and volleyball champion teams on engineering-sponsored teams.

Why did choose to come to ASU?
I grew up with ASU in my backyard practically and wanted to be a Sun Devil! Also because I knew there were plenty of great engineering programs, which I knew I wanted to pursue at the time.

What led you to choose to study engineering?
I knew I was great at math and science from an early age. Originally I was enrolled at ASU as an electrical engineering major, however I went to a talk given by the director of the School of Biological and Health Systems Engineering at the time, William Ditto, and he inspired me to make a difference in the medical space and I switched my major to biomedical engineering. During my second semester, I took my first programming class and really loved it. Not wanting to give either up, I decided to take on the challenge of completing both degrees.

Name a professor who was particularly instrumental in helping you grow as a student?
Lecturer Debra Calliss — she inspired me to stick with computer systems and helped me make the decision to include it as another degree. She also served as a role model and an outlet that I felt comfortable talking with about current struggles and also future goals.

How do you see your future?
I would love to work on embedded devices for the medical field and hopefully create something that truly helps someone someday.

Distinguished Graduates

These students have made a positive impact at ASU and in communities in Arizona through their leadership, public service, K-12 education outreach, research achievements and social entrepreneurship efforts.

Evan Hammac
BSE in Aerospace Engineering
Graduated from Highland High School in Higley, Arizona
Originally from Towcester, England

Hammac participated in the Fulton Undergraduate Research Initiative (FURI) program for two semesters. He devised a new design for a force balance that works in a sub-sonic wind tunnel, and began constructing it. It’s now used to teach fellow students about aerodynamics.

What led you to choose to study engineering and to decide on the specific major you chose?
Ever since I can remember, I have been looking up at the stars and been fascinated by how the world works. Getting involved in engineering seemed the natural progression for my life.

What has been most rewarding about your undergraduate years at ASU? What has been most challenging?
The most rewarding experience at ASU would be without a doubt FURI. I learned so much about myself and about engineering. The most challenging thing has been learning to balance life with schoolwork.

Is there a professor who has been particularly instrumental in helping you grow as a student? How and in what way did they impact you?
Lecturer Benjamin Mertz has been instrumental in my success at ASU. He was my FURI mentor and prior to that my professor for a required course in my major. It was a conversation with him that first inspired me to engage in FURI.

What great engineering achievements would you most like to be part of making happen In the future?
My long-term career aspirations are to be instrumental in a large aerospace company. I don’t quite know exactly how, but I know once I get into industry I will make quite an impact. I see my future as a very bright one. My dream is to go into space.

Peter Harper
BSE in Mechanical Engineering
Graduated from Heritage Academy
Originally from Mesa, Arizona

Peter Harper served as the chair and president of the ASU chapter of the American Society of Mechanical Engineers (ASME). He worked with a Fulton Undergraduate Research Initiative (FURI) team, helping to select and set up a gamma radiation detector to study whether lithium-ion batteries could determine where the nuclear material came from in a nuclear weapon.

What led you to choose to study engineering and to decide on the specific major you chose?
I chose to study engineering because I grew up around it. My dad worked as an engineer in the aerospace industry. I chose to major in mechanical engineering because it gives me a broad skill set and a lot of employment opportunities.

Was there a particular “Ah-Ha!” moment when you knew that you were on the right path in your college studies?
By participating in ASME, I was able to gain leadership experience and network with other students and employers. The networking experiences led to my first internship experience, which in turn has opened the door to two more internships. These internships have been valuable opportunities to not only gain experience, but also better understand what I want to do as an engineer.

Is there a professor who has been particularly instrumental in helping you grow as a student? How and in what way did they impact you?
James Middleton has helped me by encouraging me to love learning, learn from my mistakes and by answering my questions, both in class and outside of class.

What are your plans after graduation?
I will stay at ASU to earn a master’s degree in mechanical engineering through the 4+1 program. I want to work in the defense or aerospace industries. While transitioning from attending classes to looking for a full-time job is intimidating, I‘m excited about the opportunities ahead. I would love to work for an aerospace company, because each day I could look into the sky at planes flying overhead and know that I help make them fly.

Mayank “Max” Prasad
MS in Computer Engineering
Graduated from VIT University in India
Originally from New Delhi, India

Mayank Prasad came to ASU for the computer engineering curriculum and proximity to companies such as Intel, Freescale, Microchip, NXP. He was also drawn to the great entrepreneurship program. He earned an Experiential Learning Grant from Fulton Schools Startup School to attend the European Innovation Academy in Nice, France in July 2015. He works with ASU’s Office of Entrepreneurship and Innovation as an E+I ambassador, was an ASU Startup School certified facilitator and was one of the founding members of the new ASU Startup Hotline to help students with their startup-related questions.

Did you participate in any student organizations?
I started a new Fulton student organization — SPARCe (pronounced “sparky” – Students’ Project and Research Consulting in Engineering). It’s a student-run consulting group that helps engineering students get application based hands-on experience by giving them an opportunity to work on real-world projects from local businesses and non-profits. After its success, I started The Talent Network. The Talent Network makes it easier and faster for tech companies to discover and hire student developers for internship/part-time/full-time work.

Can you name a professor who was particularly instrumental in helping you grow as a student?
Yes — two actually! Lecturer Brent Sebold and Faculty Associate Ken Mulligan. Brent is the director of Fulton Schools Startup Center and Ken is with the same startup center. I took the course — FSE501 Technology Entrepreneurship with them. They helped me learn the lean launch methodology for startups and helped me convert my idea into a business. They helped me realize that entrepreneurship is a way of life. They are also my two biggest cheerleaders.

What are your plans after graduation?
I am an entrepreneur — going full-time for my startup, The Talent Network. Also maybe work part-time at a paying job until we raise seed money for my startup. In the long term, I would like to see The Talent Network become a successful company. At the same time I would like to get involved with a tech startup and help them build a revolutionary product (like internet of things), something that aligns with my purpose on this planet.

The Flexible Electronics and Display Center (FEDC) at Arizona State University and PARC, a Xerox company, announced today that they have successfully manufactured the world's largest flexible X-ray detector prototypes using advanced thin film transistors.

Measuring 10 diagonal inches, the device has been jointly developed at the ASU center and PARC in conjunction with the Army Research Lab and the Defense Threat Reduction Agency. The device will be used to advance the development of flexible X-ray detectors for use in thin, lightweight, conformable and highly rugged devices.

“This achievement is a fantastic example of how academia, industry and government can collaborate to advance key technologies and national priorities,” said Sethuraman “Panch” Panchanathan, senior vice president for Knowledge Enterprise Development at ASU. “Flexible electronics hold tremendous potential to accelerate our global competitiveness in the area of advanced manufacturing by partnering with federal agencies and industry leaders." Download Full Image

The thin film transistor and PIN diode processing was done on the 470- by 370-mm Gen II line at the Flexible Electronics and Display Center. This device showcases the center's successful scale up to GEN II, and the ability to produce sensors and displays using thin film transistors in standard process flows with the center’s proprietary bond/de-bond technology. These detectors are unique in that they showcase both of the flexible substrates the center uses to make devices. Some of the new detectors are on polyethylene naphthalate and some are on polyimide.

“This success came from a rewarding collaboration that combines FEDC’s flexible array fabrication technology and PARC’s experience with digital X-ray systems,” said Bob Street, PARC Senior Research Fellow.

The system design and integration was done at PARC. The flexible X-ray sensor was coupled to a tablet device for control and image viewing. This system shows PARC’s capability to build user-defined prototype systems incorporating novel device physics, materials and technology. PARC has extensive experience in building large-area electronic systems, display and backplane prototypes, and organic and printed electronics.

ASU media contact: Judy Keane, judy.keane@asu.edu

Two Barrett, the Honors College students have been awarded prestigious scholarships that will allow them to travel the world next year to conduct research projects of their own design.

Carlyn Harris, a junior majoring in microbiology and global health, was awarded the Circumnavigators Club Grant. From May to August 2016, Harris will travel to Guatemala, Spain, the Netherlands, India, South Africa and New Zealand to research societal and cultural influences on antibiotic consumption and resistance. Carlyn Harris, a junior honors student majoring in microbiology and global health, has won the 2016 Circumnavigators Club Grant. Download Full Image

Brigitte Nicoletti, a junior majoring in history, received the Barrett Honors Intercontinental Study Award. Also from May to August next year, she will travel to Switzerland, Norway, Germany, Malawi and Japan to study compliance with international norms of restorative justice practices advanced by the United Nations.

Each award is worth approximately $9,000 and covers the cost of travel, lodging, and research materials.

Harris and Nicoletti were assisted in their application by staff in the Lorraine W. Frank Office of National Scholarship Advisement (LWFONSA) housed at the Barrett Honors College Tempe campus. LWFONSA assists students from throughout ASU with applications for significant scholarships including Circumnavigator, Marshall, Truman, Udall and Fulbright.

According to Kyle Mox, LWFONSA director, the competition for these awards was stiff. Ten applications — each requiring a five-page proposal and letters of recommendation — were submitted. 

From the 10 applications, five finalists were chosen for interviews by a joint committee consisting of members of the Circumnavigators Club — an organization which funds the Circumnavigators Award — and a contingent of staff from Barrett Honors College and LWFONSA. The finalists were then asked to revise their applications into fully-developed 10-page proposals.

"While the applicant pools were fairly small, the overall quality of the applications was extraordinarily high. Each of the students who submitted a proposal had done a remarkable amount of background research and legwork to establish contacts in the prospective host countries," Mox said.

“Carlyn impressed the committee with her eloquence and sophisticated understanding of this important public health issue. She had previously conducted similar research in Guatemala, and she did an excellent job of explaining how the proposed research would contribute not only to her honors thesis, but her post-graduate study and career,” he said.

“Similarly, Brigitte demonstrated an impressive depth of knowledge surrounding her project, and she conducted herself with remarkable poise and comportment. The committee agreed that she would represent ASU and BHC well during her studies abroad. Her project was interesting and compelling, and her research will contribute directly to her honors thesis,” he added

“I am completely amazed and humbled that I received the grant. I am beyond grateful. Putting together the proposal and establishing contacts around the world took a lot of work but I'm thrilled to travel to new places and learn from experts in microbiology and public health fields,” Harris said.

She said her ultimate goal in assessing sociocultural ties to public health knowledge of antibiotic resistance and consumption is to develop new educational initiatives and awareness campaigns.

Harris is no stranger to international travel. In the summer of 2015, she was a research assistant in the Arizona State University Global Health Medical Anthropology Field School in Guatemala, where she helped with the investigation of maternal health care systems and family size in rural areas of that country.

This time, her research will focus another public health issue that is spreading throughout the world.

“Culture plays an important role in how societies interact with the healthcare system and what public health information they receive. I decided to study cultural influences on public health knowledge regarding antibiotic resistance and consumption because antibiotic resistance is a current global issue threatening the treatment of serious bacterial infections. This is largely because communities are overusing and misusing these 'miracle' drugs and many do not understand how this can influence resistance,” she said.

The project also will allow Harris to blend her passions of microbiology and public health.

Harris currently is an undergraduate assistant in the Biodesign Institute, researching antimicrobial therapies against Methicillin-resistant Staphylococcus aureus (MRSA), a strain of staph bacteria that has become resistant to the antibiotics commonly used to treat staph infections.

Harris is set to graduate with a bachelor’s degree in 2017. Her goal is to earn a master’s degree in public health and attend medical school. Her “dream job” would be as a medical officer for the World Health Organization or a medical adviser for a global health nonprofit benefiting underserved populations.

“For now, I'm just excited to learn all that I can and see where my experiences take me. This incredible trip will undoubtedly help me on my path and open up many opportunities,” she said.

Brigitte Nicoletti, a junior honors student majoring in history, has received the 2016 Barrett Honors Intercontinental Study Award.

Nicoletti's interest in law was sparked in ninth grade when she joined her high school's mock trial program. In eleventh grade, she began participating as a juror and attorney in Coconino County's Teen Court, a diversionary and restorative justice program for juveniles.

She brought that interest to Arizona State University where she took a class with law professor Anne Herbert called The Global Legal Community and directed a research project that examined international, regional and national approaches to juvenile justice to design a restorative juvenile justice model for Latin American countries. She is now Herbert's research and teaching assistant and is coauthoring a textbook with the professor in which she plans to incorporate her juvenile justice research. 

“I am incredibly excited to have won this award. I have been passionate about juvenile justice since participating in Teen Court back in high school,” she said.

Teen Court is not a court of law. Its goal is to determine a fair sentence for first offenders who have admitted guilt for low-level offenses rather than subject them to the mercy of the criminal justice system. In Teen Court, juvenile offenders are tried in a court of their peers that is presided over by a Superior Court Judge. The lawyers, jurors, clerks, and bailiffs are all teenagers. Sentences have ranged from referral to social services, community service, group counseling, or public apology.

“My experience with this program (Youth Court) taught me that one of the major problems with our justice system is that is fails to see juvenile offenders as individuals with the ability to grow and change. This is not only harmful to the kid, but also to the community as a whole, because it depletes it of its best resource; youth potential,” Nicoletti said

Nicoletti said she believes that by studying how other countries comply with international norms of restorative justice advanced by the United Nations in the "Convention on the Rights of the Child," she can help develop strategies for the implementation of restorative justice in the United States.

“I will examine how these international norms of restorative justice come to be incorporated in domestic legal systems. From this, I hope to gain an understanding of the reasons some countries successfully adapt international norms while others struggle to uphold even the most basic of human rights,” she said in her proposal.

“My goal is to cull best practices for international norm creation and domestic norm implementation from this research and further study how best to promote restorative juvenile justice in countries that do not meet international standards, beginning with the United States,” she added.

Nicoletti, who is set to graduate from ASU with an undergraduate degree in 2017, plans to pursue a joint juris doctorate and doctorate in criminal justice studies. "I plan to make juvenile justice my life's work," she said.