Vrendenburg Scholarship offers international research experience to engineering undergrads

SykesTeamDue to a rigid Chemical and Biomolecular Engineering curriculum, I never had the opportunity to study abroad during the normal academic year. I always felt left out, because many of my friends and peers had left school to spend their semesters in fabulous places like Amsterdam and London. Even worse, I studied French for many years in middle and high school and always longed to spend a semester in France.

 

 

One day, however, I happened to stumble across the Vredenburg Scholarship, the solution to all my woes.

Paris

Paris.

Each summer, the Vredenburg Scholarship funds 13 undergraduates to apply their engineering skills and training in international research, internships and service projects. I was fortunate enough to use my Vredenburg Scholarship to fulfill my dreams and spend this past summer researching in Paris.

I conducted researched at the historic Institut Curie, which is located in the beautiful fifth arrondissement of Paris. I was paired with a postdoctoral researcher, Dr. Kévin Carvalho, in the Sykes Lab. My project focused on the physics of myosin 1c, a molecular motor that plays important roles in endocytosis, membrane trafficking and transcription of DNA in the nucleus. Rather than working with complex systems like cells, I reconstituted actin gels in a controlled system on the exterior of liposomes. Then, in order to characterize myosin 1c, I would add the molecular motor and quantify the effects on the gel.

RollerBlading

Rollerblading.

Having been a part-time undergraduate researcher in the Denis Wirtz Lab at Hopkins over the past few years, it was so nice to have a full-time research position. With no classes taking up my time, I was finally able to immerse myself in research. I participated in a weekly journal club, attend seminars and listened to PhD Defenses (sometimes in French!).

When not researching in the lab, I spent my free time falling in love with Paris. The city is so alive during the summer, and there were always fun things to do. Whether walking through the Versailles Gardens or spending hours in Louvre, I was able to immerse myself in the French culture. One of my favorite days was when I rollerbladed with my friend Jane and thousands of other Parisians on a 12 mile course through Paris.

My summer was a truly incredibly experience. I was able to follow my passion of research to a wonderful, foreign city. How else would anyone want to spend their summer?

Learn more about the Vredenburg Scholarship.

Shaun McGovern, a senior in the Department of Chemical and Biomolecular Engineering, researches the viscoelastic properties of pancreatic cancer in the Wirtz Lab.

Work-life balance and the new baby

My wife is a second year oncology fellow and I am an MD who, in my goal of being a life-long student, has decided to get my PhD as well. My first two years as a graduate student in the Denis Wirtz lab were relatively uncomplicated in terms of devoting ample time to research. My wife worked long hours at the hospital, allowing me to work long hours at the lab. But I guess you could say that the work-life balance changes dramatically when you add a child to the scales.

Young lab assistant at work.

Young lab assistant at work.

Suddenly, the demands of life become significantly greater and more pressing and gone was the ability to work long hours in the lab. I remember the days of not lamenting my wife having to work the weekend because it meant I also got to go into lab and get some work done. Now, my wife working on the weekend means I am responsible for our little one and it is difficult to get work done when you are looking after a rambunctious 1 year old. The same holds true when my daughter is sick. While I envisioned a quiet day at home as she slept off her virus, instead I am chasing a rambunctious, fussy 1 year old.

I have often found that as I add more demands to my schedule, I respond by becoming more efficient with my time. That certainly has been the case in getting work accomplished now. Often having to pick my daughter up from daycare means I can no longer stay late in lab. And weekends are often devoted to family time. This has required me to take extra care in planning experiments and allocating time for data analysis. I am still able to get the work done but I can no longer blindly set up multi-day experiments. Instead, each week is planned out more thoroughly in advance, coordinating schedules with my wife.>

But in the end, all of the extra effort, coordinating, and busy times are well worth it. Having a daughter reminds me of the goals in life to accomplish. Even though my priorities have shifted and work is no longer at the top, it is still an important facet of life. It just now has some company.

Zev Binder is an MD and a third-year graduate student in the laboratory of Denis Wirtz, working on a new model system for the study of brain tumor cell motility.

Picture this: alumni meet up at AIChE annual

From left, Denis Wirtz, Christopher Hale and Terrence Dobrowsky

From left, Denis Wirtz, Christopher Hale and Terrence Dobrowsky

Two alumni of Johns Hopkins Institute for NanoBioTechnology. Dr. Chris Hale and Dr. Terrence Dobrowsky, recently met up with INBT co-Director Denis Wirtz at the annual meeting of the AIChE, held Nov. 3-8 in San Francisco. Chris and Terrence are currently work at Amgen and Biogen, respectively.

Chris and Terrence were both PhD students in Wirtz’s laboratory in the Department of Chemical and Biomolecular Engineering.

Fraley nets $500K Burroughs Wellcome Fund award for microfluidics work

Stephanie Fraley (Photo: Homewood Photography)

Stephanie Fraley (Photo: Homewood Photography)

A Johns Hopkins research fellow who is developing novel approaches to quickly identify bacterial DNA and human microRNA has won the prestigious $500,000 Burroughs Wellcome Fund (BWF) Career Award at the Scientific Interfaces. The prize, distributed over the next five years, helps transition newly minted PhDs from postdoctoral work into their first faculty positions.

Stephanie Fraley is a postdoctoral fellow working with Samuel Yang, MD, in Emergency Medicine/Infectious Disease at the Johns Hopkins School of Medicine and Jeff Wang, PhD, in Biomedical Engineering with appointments in the Whiting School of Engineering and the medical school. The goal of her work is to develop engineering technologies that can diagnose and guide treatment of sepsis, a leading cause of death worldwide, while simultaneously leading to improved understanding of how human cells and bacterial cells interact.

“Sepsis is an out of control immune response to infection,” Fraley said. “We are developing tools that are single molecule sensitive and can rapidly sort and detect bacterial and host response markers associated with sepsis. However, our devices are universal in that they can be applied to many other diseases.”

Fraley is using lab-on-chip technology, also known as microfluidics, to overcome the challenges of identifying the specific genetic material of bacteria and immune cells. Her technology aims to sort the genetic material down to the level of individual sequences so that each can be quantified with single molecule sensitivity.

“Bacterial DNA is on everything and contamination is everywhere, so trying to find the ones associated with sepsis is like the proverbial search for the needle in the haystack,” Fraley said. “With microfluidics, we can separate out all the bacterial DNA, so instead of a needle in a haystack, we have just the needles.”

Another advantage to Fraley’s novel technology is that it will assess all the diverse bacterial DNA present in a sample, without presuming which genetic material is important. “Bacteria are constantly evolving and becoming drug resistant,” she said. “With this technology, we can see all the bacterial DNA that is present individually and not just the strains we THINK we need to look for.”

Fraley’s award will follow her wherever her career takes her. The first two years of the prize fund postdoctoral training and that last three years help launch her professional career in academia. During the application process, she had to make a short presentation on her proposal to BWF’s panel of experts. “It was like the television show ‘Shark Tank’ but for scientists,” she laughs. “ The panelists gave me many helpful suggestions on my idea.”

Fraley earned her bachelor’s degree in chemical engineering from the University of Tennessee at Chattanooga and her doctorate in chemical and biomolecular engineering with Denis Wirtz, professor and director of Johns Hopkins Physical Sciences-Oncology Center. Wirtz is associate director for the Institute for NanoBioTechnology and Yang and Wang also are INBT affiliated faculty members.

BWF’s Career Awards at the Scientific Interface provides funding to bridge advanced postdoctoral training and the first three years of faculty service. These awards are intended to foster the early career development of researchers who have transitioned or are transitioning from undergraduate and/or graduate work in the physical/mathematical/computational sciences or engineering into postdoctoral work in the biological sciences, and who are dedicated to pursuing a career in academic research. These awards are open to U.S. and Canadian citizens or permanent residents as well as to U.S. temporary residents.

Students talk cancer nanotech at Homewood March 21

Students affiliated with the Center of Cancer Nanotechnology Excellence (CCNE) and the Physical Sciences-Oncology Center (PS-OC) at Johns Hopkins University have organized a spring mini-symposium for March 21, 10 a.m. in the Hackerman Hall Auditorium at the Johns Hopkins University Homewood campus.

The student-run mini-symposiums aim to bring together researchers from across the campus affiliated with the PS-OC and CCNE. Graduate students training in these centers, both administered by Johns Hopkins Institute for NanoBioTechnology, work in various disciplines from physics to engineering to the basic biological sciences but with an emphasis on understanding cancer metastasis and developing methods for cancer diagnosis or therapy.

The invited speaker for the symposium is postdoctoral researcher Megan Ho of Duke University. Ho earned her PhD in mechanical engineering in the Wang lab in 2008. She is currently focused on developing microfluidic devices to investigate and control the fundamental reactions that form nanocomplexes for gene delivery. (10 a.m.)

Student apeakers, who will talk for 15 minutes, include:

  • Jane Chisholm (Justin Hanes lab/Ophthalmology): Cisplatin nanocomplexes for the local treatment of small cell lung cancer (10:20 a.m.)
  • Yunke Song (Jeff Wang Lab/Mechanical Engineering): Single Quantum Dot-Based Multiplexed Point Mutation Detection by Gap Ligase Chain Reaction (10:35 a.m.)
  • Andrew Wong (Peter Searson Lab/Materials Science and Engineering): Intravisation into an artificial blood vessel (10:50 a.m.)
  • Brian Keeley: (Jeff Wang Lab/Mechanical Engineering): Overcoming detection limitations of DNA methylation in plasma and serum of cancer patients through utilization of nanotechnology. (11:05 a.m.)
  • Sebastian Barretto (Sharon Gerecht Lab/Chemical and Biomolecular Engineering): Development of Hydrogel Microfibers to Study Angiogenesis (11:20 a.m.)

View the symposium flyer here. The mini-symposium is free and open to the entire Johns Hopkins University community. No RSVP is required, although seating is limited.

Johns Hopkins Physical Sciences-Oncology Center

Center of Cancer Nanotechnology Excellence

Money makes the (research) world go ‘round

Photo Illustration by Mary Spiro.

Grant money drives research, but obtaining funding can be a daunting task for those unfamiliar with the process. Wouldn’t it be nice to have someone to show you the ropes?

That’s why three postdoctoral fellows from Johns Hopkins Institute for NanoBioTechnology were asked to present a sort of crash course in how to get those almighty research dollars. The talk, given as one of INBT’s professional development seminars on July 27 to a group of graduate, undergraduate and a few high school summer research interns, covered basics, as well as some commonly overlooked issues encountered in the grant application process.

“When applying for grant funds you have to assume that everyone else also has a good idea. Your idea has to be better than great; it has to be outstanding,” Eric Balzer told attendees. Balzer is a postdoctoral fellow with professor Konstantinos Konstantopoulos in the department of Chemical and Biomolecular Engineering.

He also advised the group to avoid novice grant writing errors such as “submitting a proposal on lung cancer to an agency that only funds breast cancer research.” In other words, read the funding agency’s mission statement.

Yanique Rattigan stressed the importance of avoiding overly complex language in grant applications. “Grant reviewers often include patient representatives who are not scientists and engineers, so you have to make sure that there is a section describing the research in lay terms that they can understand,” offered Rattigan, who is conducting research in the pathology lab of professor Anirban Maitra at the Johns Hopkins School of Medicine.

Granting agencies look to fund novel research ideas, explained Daniele Gilkes. “They want to know how your work will fill in the knowledge gaps that exist in the field. You can determine this through thorough analysis of the current literature pertinent to your area of research,” added Gilkes, who works with Denis Wirtz, the Smoot Professor of Engineering in the Department of Chemical and Bimolecular Engineering.”

The group stressed the need to edit and re-edit a grant application prior to submission, and emphasized the importance of choosing the right referee to compose letters that truly support the candidates potential for independent research.

The teams’ insight into the grant application process can be found in this SlideShare slide show, click here.

Story by Mary Spiro.

 

 

 

 

 

 

 

 

 

 

 

 

Nanobio postdocs offer trusted tips on getting grant money

Photo illustration by Mary Spiro.

Three postdoctoral fellows from Johns Hopkins Institute for NanoBioTechnology will offer a one-hour crash course in how to get those research dollars; July 27, 11 a.m. Krieger 205. Free for Hopkins community.

Funding dollars make the research world go ‘round. Few know that better than postdoctoral fellows, who would be out of work without it. As part of Johns Hopkins Institute for NanoBioTechnology’s last professional development seminar of the summer, three INBT affiliated postdoctoral fellows will offer their sage advice on preparing winning research grants.

Topics to be covered on the basic aspects of grant writing include:

  • knowing when to write a grant
  • identifying funding sources
  • planning a timeline
  • how to structure a competitive proposal
  • do’s and dont’s of grant writing and planning
  • basic science writing tips for conveying ideas clearly and succinctly

This seminar will be led by Eric Balzer, postdoctoral fellow with professor Konstantinos Konstantopoulos (ChemBE); Yanique Rattigan, postdoctoral fellow with professor Anirban Maitra (Oncology/Pathology); and Daniele Gilkes, postdoctoral fellow with professor Denis Wirtz (ChemBE).

For additional information on INBT’s professional development seminar series, contact Ashanti Edwards, INBT’s Academic Program Administrator at Ashanti@jhu.edu.

 

 

 

 

Summer interns join PS-OC labs

Each summer, Johns Hopkins Institute for Nanobiotechnology (INBT) hosts several summer research interns, five of who will conduct research as part of Johns Hopkins Physical Sciences-Oncology Center.

Erin Heim, from University of Florida, will be testing the effects of cell geometry and chemotaxis on cell polarity in the Denis Wirtz lab (Chemical and Biomolecular Engineering). “The goal is to find which of the two is more important to polarity when working against each other,” she said.

Also in the Wirtz lab, Nick Trenton is developing an agarose-based microfluidics chamber that can be used to establish a chemotaxis gradient in 3D cell culture. “We’ll be testing various cell knockdowns in 3D in the presence of a chemokine gradient,” he said.

Rachel Louie from Johns Hopkins, works in the Peter Searson lab (Materials Science and Engineering). She is characterizing the properties of human umbilical vein endothelial cells cultured under different conditions. “We’re testing to see how the amount of growth factors in cell culture medium will affect transendothelial electrical resistance values,” Louie said.

Thea Roper from North Carolina State University works in the Sharon Gerecht lab (Chemical and Biomolecular Engineering). Roper said she will analyze how human embryonic stem cells mature into smooth muscle cells. “To do this, I must determine the pathway by using techniques such as immunofluorescence, RT-PCR, and Western Blot to examine Myocardin, a transcriptional co-activator, Elk-1, a ternary complex factor, PDGF-R, platelet-derived growth factor receptors, and SRF, serum response factors,” she said.

Quinton Smith also works in the Gerecht lab. This is his second year interning at Hopkins. Smith, from University of New Mexico, is fabricating a microfluidic device that recreates hypoxic (low oxygen) conditions. “I’ll study how adult and embryonic stem cells respond to this dynamic environment,” he said.

Read more about INBT’s summer interns at the following link: http://wp.me/p1sSPo-VT

 

Hopkins alumni learn about engineering in oncology

Denis Wirtz directs INBT’s Engineering in Oncology Center. Photo: Mary Spiro

As  part of Johns Hopkins Alumni Weekend 2011, Denis Wirtz, director of the Johns Hopkins Engineering in Oncology Center, gave a talk April 29 on how researchers are using physics and engineering to better understand cancer. Wirtz is the Theophilus H. Smoot Professor in the Whiting School of Engineering Department of Chemical and Biomolecular Engineering.

Wirtz spoke in Mason Hall Auditorium with about 100 alumni in attendance. He showed animations explaining the process of metastasis and concluded his remark with a viewing of the short movie “INBT: An Overview.” The audience seemed engaged and asked several questions following Wirtz’s presentation. The talk was presented for the Class of ’61 alumni.

Johns Hopkins Engineering in Oncology Center is a Physical Sciences-Oncology Center funded by the National Cancer Institute. It was established in 2009.

To see the full gallery of photos from this event, visit this link on the PS-OC  Facebook page.

Cells studied in 3-D may reveal novel cancer targets

Stephanie Fraley

Stephanie Fraley, a doctoral student in chemical and biomolecular engineering, was lead author of the study. Photo by Will Kirk/HomewoodPhoto.jhu.edu

Showing movies in 3-D has produced a box-office bonanza in recent months. Could viewing cell behavior in three dimensions lead to important advances in cancer research? A new study led by Johns Hopkins University engineers indicates it may happen. Looking at cells in 3-D, the team members concluded, yields more accurate information that could help develop drugs to prevent cancer’s spread.

“Finding out how cells move and stick to surfaces is critical to our understanding of cancer and other diseases. But most of what we know about these behaviors has been learned in the 2-D environment of Petri dishes,” said Denis Wirtz, director of the Johns Hopkins Engineering in Oncology Center and principal investigator of the study. “Our study demonstrates for the first time that the way cells move inside a three-dimensional environment, such as the human body, is fundamentally different from the behavior we’ve seen in conventional flat lab dishes. It’s both qualitatively and quantitatively different.”

One implication of this discovery is that the results produced by a common high-speed method of screening drugs to prevent cell migration on flat substrates are, at best, misleading, said Wirtz, who also is the Theophilus H. Smoot Professor of Chemical and Biomolecular Engineering at Johns Hopkins. This is important because cell movement is related to the spread of cancer, Wirtz said. “Our study identified possible targets to dramatically slow down cell invasion in a three-dimensional matrix.”

When cells are grown in two dimensions, Wirtz said, certain proteins help to form long-lived attachments called focal adhesions on surfaces. Under these 2-D conditions, these adhesions can last several seconds to several minutes. The cell also develops a broad, fan-shaped protrusion called a lamella along its leading edges, which helps move it forward. “In 3-D, the shape is completely different,” Wirtz said. “It is more spindlelike with two pointed protrusions at opposite ends. Focal adhesions, if they exist at all, are so tiny and so short-lived they cannot be resolved with microscopy.”

The study’s lead author, Stephanie Fraley, a Johns Hopkins doctoral student in Chemical and Biomolecular Engineering, said that the shape and mode of movement for cells in 2-D are merely an “artifact of their environment,” which could produce misleading results when testing the effect of different drugs. “It is much more difficult to do 3-D cell culture than it is to do 2-D cell culture,” Fraley said. “Typically, any kind of drug study that you do is conducted in 2D cell cultures before it is carried over into animal models. Sometimes, drug study results don’t resemble the outcomes of clinical studies. This may be one of the keys to understanding why things don’t always match up.”

collagen fibers

Reflection confocal micrograph of collagen fibers of a 3D matrix with cancer cells embedded. Image by Stephanie Fraley/Wirtz Lab

Fraley’s faculty supervisor, Wirtz, suggested that part of the reason for the disconnect could be that even in studies that are called 3-D, the top of the cells are still located above the matrix. “Most of the work has been for cells only partially embedded in a matrix, which we call 2.5-D,” he said. “Our paper shows the fundamental difference between 3-D and 2.5-D: Focal adhesions disappear, and the role of focal adhesion proteins in regulating cell motility becomes different.”

Wirtz added that “because loss of adhesion and enhanced cell movement are hallmarks of cancer,” his team’s findings should radically alter the way cells are cultured for drug studies. For example, the team found that in a 3-D environment, cells possessing the protein zyxin would move in a random way, exploring their local environment. But when the gene for zyxin was disabled, the cells traveled in a rapid and persistent, almost one-dimensional pathway far from their place of origin.

Fraley said such cells might even travel back down the same pathways they had already explored. “It turns out that zyxin is misregulated in many cancers,” Fraley said. Therefore, she added, an understanding of the function of proteins like zyxin in a 3-D cell culture is critical to understanding how cancer spreads, or metastasizes. “Of course tumor growth is important, but what kills most cancer patients is metastasis,” she said.

To study cells in 3-D, the team coated a glass slide with layers of collagen-enriched gel several millimeters thick. Collagen, the most abundant protein in the body, forms a network in the gel of cross-linked fibers similar to the natural extracellular matrix scaffold upon which cells grow in the body. The researchers then mixed cells into the gel before it set. Next, they used an inverted confocal microscope to view from below the cells traveling within the gel matrix. The displacement of tiny beads embedded in the gel was used to show movement of the collagen fibers as the cells extended protrusions in both directions and then pulled inward before releasing one fiber and propelling themselves forward.

Fraley compared the movement of the cells to a person trying to maneuver through an obstacle course crisscrossed with bungee cords. “Cells move by extending one protrusion forward and another backward, contracting inward, and then releasing one of the contacts before releasing the other,” she said. Ultimately, the cell moves in the direction of the contact released last.

When a cell moves along on a 2-D surface, the underside of the cell is in constant contact with a surface, where it can form many large and long-lasting focal adhesions. Cells moving in 3-D environments, however, only make brief contacts with the network of collagen fibers surrounding them–contacts too small to see and too short-lived to even measure, the researchers observed.

“We think the same focal adhesion proteins identified in 2-D situations play a role in 3-D motility, but their role in 3-D is completely different and unknown,” Wirtz said. “There is more we need to discover.”

Fraley said her future research will be focused specifically on the role of mechanosensory proteins like zyxin on motility, as well as how factors such as gel matrix pore size and stiffness affect cell migration in 3-D.

Co-investigators on this research from Washington University in St. Louis were Gregory D. Longmore, a professor of medicine, and his postdoctoral fellow Yunfeng Feng, both of whom are affiliated with the university’s BRIGHT Institute. Longmore and Wirtz lead one of three core projects that are the focus of the Johns Hopkins Engineering in Oncology Center, a National Cancer Institute-funded Physical Sciences in Oncology Center. Additional Johns Hopkins authors, all from the Department of Chemical and Biomolecular Engineering, were Alfredo Celedon, a recent doctoral recipient; Ranjini Krishnamurthy, a recent bachelor’s degree recipient; and Dong-Hwee Kim, a current doctoral student.

Funding for the research was provided by the National Cancer Institute.  This study, a collaboration with researchers at Washington University in St. Louis, appeared in the June issue of Nature Cell Biology.

Related links:

Johns Hopkins Engineering in Oncology Center

Department of Chemical and Biomolecular Engineering

Watch a related video on YouTube

Story by Mary Spiro