Tag: malaria

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Bioengineering Round-Up (January 2020)

by Sophie Burkholder

University of Washington Researchers Engineer a New Way to Study Circulatory Obstruction

Capillaries are one of the most important forms of vasculature in our body, as they allow our blood to transfer nutrients to other parts of our body. But for how much effect capillary functionality can have on our health, their small size makes them extremely difficult to engineer into models for a variety of diseases. Now, researchers at the University of Washington led by Ying Zheng, Ph. D., engineered a three-dimensional microvessel model with living cells to study the mechanisms of microcirculatory obstruction involved with malaria.

Rather than just achieving a physical model of capillaries, these researchers created a model that allowed them to study typical flow and motion through capillaries, before comparing it to deficiencies in this behavior involved with diseases like malaria. The shape of the engineered model is similar to that of an hourglass, allowing the researchers to study instances where red blood cell transit may encounter bottlenecks between the capillaries and other vessels. Using multiphoton technology, Zheng and her team created 100mm capillary models with etched-in channels and a collagen base, to closely model the typical size and rigidity of the vessels. Tested with malaria-infected blood cells, the model showed similar circulatory obstructive behavior to that which occurs in patients, giving hope that this model can be transferred to other diseases involving such obstruction, like sickle cell anemia, diabetes, and cardiovascular conditions.

Understanding a Cell Membrane Protein Could Be the Key to New Cancer Treatments

Almost every cell in the body has integrins, a form of proteins, on its membrane, allowing cells to sense biological information from beyond their membranes while also using this feedback information to initiate signals within cells themselves. Bioengineers at the Imperial College of London recently looked at the way another membrane protein, called syndecan-4, interacts with integrins as a potential form of future cancer treatment. Referred to as “cellular hands” by lead researcher of the study Armando del Rio Hernandez, Ph.D., syndecan-4 sometimes controls the  development of diseases or conditions like cancer and fibrosis. Hernandez and his team specifically studied the ties of syndecan-4 to yes-associated protein (YAP) and enzyme called P13K, both of which are affiliated with qualities of cancer progression like halted apoptosis or cell stiffening. Knowing this, Hernandez and his team hope to continue research into understanding the mechanisms of syndecan-4 throughout the cell, in search of new mechanisms and targets to focus on with future developments of cancer treatments.

A New Medical Device Could Improve Nerve Functionality After Severe Damage

Serious nerve damage remains difficult to repair surgically, often involving the stretching of nerves for localized damage, or the transfer of healthy nerve cells from another part of the body to fill larger gaps in nerve damage. But these imperfect solutions limit the return of full nerve function and movement to the damaged part of the body, and in more serious cases with large areas of nerve damage, can also risk damage in other areas of the body that healthy nerves are borrowed from for treatment. A new study from the University of Pittsburgh published in Science Translational Medicine led by Kacey Marra, Ph. D., has successfully repaired nerve damage in mice and monkeys using a biodegradable tube that releases growth factors called glial-cell-derived neurotrophic factors over time.

Marra and her team showed that this new device restored nerve function up to 80% in nonhuman primates, where current methods of nerve replacement often only achieve 50-60% functionality restoration. The device might have an easier time getting FDA-approval, since it doesn’t involve the use of stem cells in its repair mechanisms. Hoping to start human clinical trials in 2021, Marra and her team hope that the device will help both injured veterans and typical patients with nerve damage, and see potential future applications in facial nerve damage as well.

A New Computational Model Could Improve Treatments for Cancer, HIV, and Autoimmune Diseases

With cancer, HIV, and other autoimmune diseases, the best treatment options for patients are often determined with trial-and-error methods, leading to prolonged instances of ineffective approaches and sometimes unnecessary side effects. A group of researchers led by Wesley Errington, Ph.D., at the University of Minnesota decided to take a computational approach this problem, in an effort to more quickly and efficiently determine the most appropriate treatment for a given patient. Based on parameters controlling interactions between molecules with multiple binding sites, the team’s new model looks primarily at binding strength, linkage rigidity, and size of linkage arrays. Because diseases can often involve issues in molecular binding, the model aimed to model the 78 unique binding configurations for cases of when interacting molecules only have three binding sites, which are often difficult to observe experimentally. This new approach will allow for faster and easier determination of treatments for patients with diseases involving these molecular interactions.

Improved Drug Screening for Glioblastoma Patients

A new microfluidic brain chip from researchers at the University of Houston could help improve treatment evaluations for brain tumors. Glioblastoma patients, who have a five-year survival rate of a little over 5%, are some of the most common patients suffering from malignant brain tumors. This new chip, developed by the lab of Yasemin Akay, Ph.D., can quickly determine cancer drug effectiveness by analyzing a piece of cultured tumor biopsy from a patient by incorporating different chemotherapy treatments through the microfluidic vessels. Overall, Akay and her team found that this new chip holds hope as a future efficient and inexpensive form of drug screening for glioblastoma patients.

People and Places

The brain constructs maps to guide people, not just of physical spaces but also to connect stimuli around them, like conversations and other people. It’s long been known that the brain area responsible for this spatial navigation—the medial temporal lobe—is also involved in recalling memories.

Michael Kahana (left) is principal investigator in the Defense Advanced Research Projects Agency’s RAM program and a professor in the Department of Psychology. Ethan Solomon is an M.D./Ph.D. student in the Department of Bioengineering of the School of Engineering and Applied Science and in the Perelman School of Medicine.

Now, neuroscientists at the University of Pennsylvania have discovered that the signals the brain produces during spatial navigation and episodic memory recall look similar. Low-frequency brain waves called the theta rhythm appear as people jump from one memory to the next, as many prior studies looking only at human navigation have shown. The new findings, which suggest that the brain structures responsible for helping people navigate the world may also “navigate” a mental map of prior experiences, appear in the Proceedings of the National Academy of Sciences.

Read the rest of this story featuring Penn Bioengineering’s Graduate Group member Michael Kahana and M.D./Ph.D. student Ethan Solomon on Penn Today.

The Florida Institute of Technology recently announced plans to start construction in spring 2020 on a new Health Sciences Research Center, set to further establish biomedical engineering and pre-medical coursework and research at the institute. With plans to open the new center in 2022, Florida Tech anticipates increased enrollment in the two programs, and hopes that the center will offer more opportunities in a growing professional field.

Anson Ong, Ph.D., the Associate Dean of Administration and Graduate Programs at the University of Texas at San Antonio, was recently elected to the International College of Fellows of Biomaterials Science and Engineering. With a focus on research in biomaterial implants for orthopaedic applications, Ong’s election to the college honors his advancement and contribution to the field of biomaterials research.

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Week in BioE (September 15, 2017)

A Closer Look

7T-MRI
Seven-tesla MRI of the porcine mitral valve showing the papillary muscle (PM) and chordae tendinae (CT).

Since its invention in the early 1970s, magnetic resonance imaging (MRI) has played an increasingly important role in the diagnosis of illness. In addition, over time, the technology of MRI has evolved enormously, with the ability to render more detailed three-dimensional images using stronger magnetic fields . However, imaging tissues under mechanical loads (e.g., beating heart, lung breathing) are still difficult to image precisely with MRI.

A new study in PLOS One, led by Morten Jensen, Ph.D., of the University of Arkansas, breaks an important technical barrier in high resolution imaging for tissues under mechanical load. Using 3D-printed mounting hardware and 7-tesla MRI, this group produced some of the highest quality images yet produced of the mitral valve exposed to physiological pressures (see above). In the longer term, this method could point to new corrective surgical procedures that would greatly improve the repair procedures for mitral valves.

Oncology Breakthroughs

Among the most significant challenges faced by surgical oncologists is developing a ‘clear margin,’ meaning that the tissue remaining after tumor excision is free of any tumor cells. If the margins are not free of tumor cells, the cancer is more likely to recur. However, until now, it has been impossible to determine if cancer cells were still present in tissue margins before finishing surgery because of the time required to test specimens.

At the University of Texas, Austin, however, scientists are getting closer to overcoming this obstacle. In a recent study published in Science Translational Medicine, this team of scientists presents the MasSpecPen — short for mass spectrometry pen. This device is capable of injecting a tiny drop of water into tissue, extracting the water after it mixes with the tissue, and quickly analyzing the sample’s molecular components. The authors, who included biomedical engineering faculty member Thomas E. Milner, Ph.D., tested the device using ex vivo samples from 253 patients with different varieties of cancer, including breast, lung, and thyroid cancers. The MasSpecPen provided sensitivity, specificity, and accuracy exceeding 96% in all cases. Although it has yet to be tested intraoperatively, if effective under those conditions, the device could become an essential part of the surgeon’s arsenal.

If the MasSpecPen could render surgical treatment of cancer more effective, a device developed at SUNY Buffalo could help doctors diagnose lung cancer earlier. Lung cancer is a particularly deadly variety of cancer because patients don’t feel any discomfort until the cancer has spread to other areas of the body. In collaboration with Buffalo’s Roswell Park Center Institute, microchip manufacturer Intel, and local startup Garwood Medical Devices, a team of scientists, including Professor Edward P. Furlani, Ph.D., from Buffalo’s Department of Chemical and Biomedical Engineering, was awarded a grant from the National Science Foundation to develop a subcutaneous implant incorporating a nanoplasmonic biochip to detect biomarkers of lung cancer. A wearable smart band would receive data from the biochip and would act as an early warning system for lung cancer. The biomarkers selected for the biochip would optimally predict lung cancer risk much earlier than the metastasis stage. If the system that the team develops is successful in diagnosing lung cancer before it spreads, it could greatly improve survival and cure rates.

Feverish Growth

Worldwide but particularly in the Global South, malaria remains a major public health concern. According to a Global Burden of Disease study in 2015, there were nearly 300 million cases of the disease in a single year, with 731,000 fatalities. One of the earliest treatments to combat malaria was invented by British colonialists, who added quinine to the tonic used in the gin and tonic cocktail. More recently the drug artemisinin was developed for fighting malaria. However, this drug and its derivatives are very expensive. The primary reason for this cost is that the drug is extracted from the sweet wormwood plant, which is in short supply. In hopes of producing a greater supply of artemisinin, scientists collaborating among Denmark, Malaysia, and the Netherlands report in Frontiers in Bioengineering and Biotechnology that transplanting the genes responsible for producing atremisinin into Physcomitrella patens, a common moss, led to a much faster production rate of the drug than what is possible with the wormwood plant. The process proved simpler and less expensive than earlier attempts to transplant genes into tobacco plants. If this potential is harnessed correctly, it could make an enormous difference in lessening the global burden of malaria. 

Understanding Fear

We’ve known for years about the flight-or-fight response — the adrenergic response of our bodies to danger, which we share in common with a number of other animals. Once the decision to flee is made, however, we know far less about what determines the escape strategy used. According to Malcolm A. MacIver, professor of biomedical engineering and mechanical engineering in Northwestern University’s McCormick School of Engineering, part of the escape strategy depends on how far away the attacker is. In a paper he coauthored that was published in Current Biology, Dr. MacIver studied threat responses in larval zebrafish and found that a fast-looming stimulus produced either freezing or escape at a shorter interval following the threat perception; when the perceived threat was slow looming, longer latency following the perception of the threat was seen, resulting in a greater variety of types of escape behaviors. While it might seem a giant leap between observing behaviors in fish and higher life forms, the basic mechanism in the “oldest” parts of the brain, from an evolutionary standpoint, are less different than we might think.

People and Places

The University of Maryland has announced that construction on a new building to serve as the home of its Department of Bioengineering will be finished by the end of September. The building is to be named A. James Clark Hall, after a builder, philanthropist, and alumnus of Maryland’s School of Engineering. Further south, George Mason  University in Fairfax, Va., has announced that the new chair of its Department of Engineering there will be Michael Buschmann, Ph.D., an alumnus of MIT and faculty member since the 1990s at École Polytechnique in Montreal. Congratulations, Dr. Buschmann!