Looking Back on 2017

Happy New Year! As we welcome 2018, let’s reflect on some of the great things that happened during 2017.

Salaita Group Research on “Picky Platelets” Featured in Medical Express

Khalid Salaita
Khalid Salaita

Research from the Salaita Group is featured in a review in Medical Express. Written by Emory’s own Carol Clark, the article gives an overview of two recent journal publications covering important results related to triggering clotting in blood platelets.

“We show conclusively that, in order to activate clotting, the cell needs a targeted force of a magnitude of just a few piconewtons—or a force about a billion times less than the weight of a staple,” says Khalid Salaita, associate professor in Emory University’s Department of Chemistry and the lead author of the studies. “The real surprise we found is that platelets care about the direction of that force and that it has to be lateral. They’re very picky. But they should be picky because otherwise they might accidentally create a clot. That’s what causes strokes.”

Read the full review, and find links to the journal articles, at the link.

Update 12/20/17: Additional coverage in Science Daily!

Victor Ma Receives Predoctoral to Postdoctoral Fellow Transition Award

Victor Ma, a fourth-year graduate student in the lab of Dr. Khalid Salaita, was recently selected as one of twenty-six Predoctoroal to Postdoctoral Fellow Transition Award Fellows from the National Institute of Health. This award will provide Victor with two years of funding to complete his doctoral thesis and an additional four years of funding for future postdoc training. In the Salaita lab, with co-mentorship by Dr. Brian Evavold, Victor’s research focuses on developing technologies to study mechanobiology at the molecular scale. With an ultimate goal of establishing an alternative mechanism for regulating T cell activity, he studies the roles of mechanical forces in T cell activation, whether these forces are coordinately controlled by mechano-sensitive proteins, and the importance of these forces for T cell biological function. The findings from these studies can provide insight into a potential strategy for developing effective immunotherapies.

In his postdoc, Victor plans on transitioning into the field of tumor immunology, where he hopes to capitalize on his skillset to elucidate the physical mechanisms responsible for preventing T cells from interacting with tumor cells. “My ultimate career goal is to become an independent investigator at a research-intensive university, where I can assume teaching duties and direct a research lab that combines knowledge from various disciplines to innovate career research,” says Victor. “This award will surely serve as a stepping stone to help achieve my goal!”

Congratulations, Victor!

Congratulations, Dr. Galior!

Kornelia poses with her group and her best friend after a successful defense.
Kornelia poses with her group and her best friend after a successful defense.

Kornelia Galior successfully defended her thesis, “Protein-Based Tension Probes: From Mapping Integrin Adhesion Forces to the Mechanopharmacology of Smooth Muscle Cells” on Wednesday, April 12th, 2017. Kornelia’s thesis committed was led by Khalid Salaita with Vince Conticello and David Lynn as additional members.

During her time at Emory, Kornelia received two Quayle awards. She will start a clinical chemistry fellowship at the Mayo Clinic in July.

Congratulations, Kornelia!

Graduate Student Spotlight: Yang Liu Develops a New Method for Chemistry with “Roots” in Biology

Yang Liu in the lab. Photo provided by Yang Liu.
Yang Liu in the lab. Photo provided by Yang Liu.

Yang Liu (Salaita Group) is bringing new techniques to the emerging field of mechanobiology; at the same time, he’s returning to his roots.

Literally. As in, plants.

Yang’s father is an academic biologist studying agriculture in China.

“I think in the beginning, my dad really wanted me to be a biologist,” says Yang. “But normally kids don’t want to pursue the same career path as their parents.”

As an undergraduate in China, Yang started out studying mechanical engineering. Then, he attended a general chemistry lecture with a famous chemistry professor who made a convincing case for the importance of the discipline. “He said, ‘chemistry is the central science connecting physical sciences, life sciences and applied sciences all together,’’ says Yang. “And I was so fascinated by it. And I changed my major.”

At Emory, Yang joined the lab of Khalid Salaita. His research in the Salaita Group takes a novel approach to a common scientific question: how does the immune system recognizes and eliminates “invaders”, such as pathogens or cancer cells? Most research explores how chemical signals mediate this process. Yang’s work expands on existing work in the Salaita Group that focuses on mechanical signaling—the way that immune cells physically probe their targets within the body. “Cells can touch and apply forces to one another,” explains Yang, a process he refers to as a “handshake.” Yang’s research develops tools that allow scientists to “see” these kinds of physical interactions.

Gold nanoparticle (yellow) with elastic spring molecules (gray) bound to a fluorophore and ligand (black). When a ligand binds to a membrane receptor (cyan), the spring “pulls” and the fluorophore elicits a signal (bright white).
Gold nanoparticle (yellow) with elastic spring molecules (gray) bound to a fluorophore and ligand (black). When a ligand binds to a membrane receptor (cyan), the spring “pulls” and the fluorophore elicits a signal (bright white). Photo provided by Yang Liu.

Specifically, Yang has developed a technique named molecular tension fluorescence microscopy (MTFM) that employs single elastic molecules—DNA, protein, and polymer— as sensors to visualize membrane receptor mediated forces at the piconewton level. “One piconewton is the weight of one trillionth of an apple and surprisingly, pN forces regulate biochemical signaling pathways,” says Yang. These forces are too small for scientists to measure using conventional methods. Existing tools aren’t sensitive enough or they are inefficient.

“Until our method kicks in,” says Yang.

Yang has combined nanotechnology and the “easy” surface chemistry of gold nanoparticles to make MTFM probes more effective. “These gold particle sensors are spring scales at nanoscale ,” says Yang. “Compared to previous techniques, these probes are of significantly enhanced sensitivity, stability and amenable for detecting forces mediated by almost all kinds of cell receptors.”

The improvements have caught the attention of researchers in other Emory units—and even nationally and internationally. Yang has collaborated with the Evavold Lab in the Department of Immunology at Emory to help them measure mechanical forces mediated by different immune cells. He also has collaborators from as far away as New York and Germany.

Regarding these collaborations, Yang says: “The need to be trained [to use this method] is very high. The method is not hard, it’s easy. So people usually spend a few days and they should be able to master it…and we still maintain quite tight collaboration. We not only teach them how to make it, we actually get involved in the scientific questions they care about and continue this collaboration.”

Recently, Yang’s success in developing the new method was recognized with the department’s highest graduate student honor, the Quayle Outstanding Student Award. Speaking of Yang’s progress shortly after the award ceremony, advisor Khalid Salaita praised Yang’s work ethic as well as his science: “Yang was a real pleasure to have in the lab. He was incredibly thoughtful, well read, and intensely motivated. More than anyone else I’ve worked with, Yang displayed a keen instinct for experimental design. He spent countless hours in the dark microscope room collecting data and working around the clock fueled up with his favorite bbq Pringles and excited by the science.”

The award ceremony was followed swiftly by another milestone—a successful PhD defense. Next, Yang is headed to John’s Hopkins University where he will work in the lab of Dr. Taekjip Ha, a world leader in the development of single molecule fluorescence microscopy and force spectroscopy.

Salaita Group "Logo"
Salaita Group Logo

Yang’s pioneering research wasn’t always smooth sailing. “I didn’t get my first experiment done until the first semester of my third year. Everything before that didn’t work.” He credits his perseverance to his father’s example—“agriculture is even slower, waiting for the growth of plants. You can only do two experiments a year!”—as well as his own scientific curiosity. His advisor, Khalid Salaita, was also an inspiration throughout the process. “He is always passionate and ignited my love for science. You love it and you work hard to make something meaningful to the society and also make yourself valuable, so, that’s what I’d like to do and that’s because of these two people.”

Does all this mean that Yang has overcome his initial reluctance to follow in his father’s footsteps towards biology?

“I think I’m going back to the route, mining chemistry, biology. In the beginning I was against it, but I do like it.” Still, chemistry has his heart. “Chemists not only create new tools, new theories and new materials, but also create new opportunities. And if you want to study biology as a chemist, there are some advantages too because you can understand and explore the secret of life at the molecular level.”

Graduate student Yun Zhang wins poster prize

Chemistry graduate student Yun Zhang (Salaita Group) received an award for “Best Poster” at the 2015 Gordon Research Conference “Fibronectin, Integrins & Related Molecules.” The conference, a key scientific meeting for those interested in integrins and the interactions between cells with the extracellular matrix in development, homeostasis and disease, took place February 10th – 15th at the Ventura Beach Marriott, Ventura, California.

Zhang’s poster was presented as part of the session “”Mechanobiology and Matrix Dynamics.” The full abstract for the poster appears below:

Mapping integrin forces with high spatial and temporal resolution during platelet activation

Yun Zhang, Yongzhi Qui, Wilbur Lam, Khalid Salaita

Platelets play an essential role in hemostatic response by forming blood clots that seal the damaged vessel sites and promote vascular healing. Through the coordination of physical-chemical interaction between integrin aIIbb3, actin, and myosin, platelets adhere and generate forces to strengthen their adhesion to the exposed extracellular matrix and fibrin mesh. Recent work suggests that platelets sense the stiffness of their extracellular matrix and respond by tuning their activation levels. Nonetheless, a fundamental question pertaining to the role of mechanics in platelet activation is whether the aIIbb3 integrins experience mechanical tension during activation and its precise magnitude, and spatial and temporal distribution during platelet activation. To address this question, we first immobilized integrin ligands onto a supported lipid membrane and found that laterally mobility markedly dampens the activity of ligands for aIIbb3   integrins. Next, we developed DNA-based fluorescence tension probes to visualize piconewton scale forces during platelet activation cascades. These probes provided the highest resolution force maps associated with platelet activation to date. Interestingly, we found that platelets exert force through filopodia nearly instantaneously when activated by contact with the sensor surface. As filopodia coalesced to form circumferential lamellae, the tension was greatly increased and specifically accumulated at the cell periphery and the center of the cell area. The tension at the center of the platelet was highly influenced by myosin contractility. Finally, By comparing the tension signal associated with a small library of integrin ligands that bind aIIbb3, we found that platelet-generated forces are highly dependent on the chemical identify of the ligands. For example, cyclic RGD ligands experience over 19 pN of tension, whereas the HHLGGAKQAGD ligand experience values of tension greater than 2.4 pN but lower than 4.2 pN. Taken together, this data demonstrates that mechanical forces play a critical role in platelet activation and newly emerging molecular tension probes provide a power approach to elucidate the role of integrin tension in platelet activation. This may potentially guide new hemostatic or antithrombotic treatments.