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Biology subjects

Gracias, D.

Publications and source records attributed to Gracias, D..

3 recordsLinked to original sources

Shape-shifting microgel automata controlled by DNA sequence instructions

Controlling material shapes using information-bearing molecular signals is central to the creation of autonomous, reconfigurable soft devices. While physical and chemical stimuli can direct simple material swelling, bending, or folding, it has been challenging to direct multi-step shape-change programs crucial for complex, robotic tasks. Here, we demonstrate gel automata-- sub-millimeter, photopatterned, highly swellable DNA gels--whose parts grow or shrink in response to easily designed DNA activator sequences, allowing for precisely controlled device articulation. We design and fabricate gel automata that reversibly transform between different letter shapes, and use neural networks to design automata that transform into every even or every odd numeral via designed reconfiguration programs. This sequential and repetitive metamorphosis of materials via chemical reorganization could dramatically advance our ability to manipulate micro-particles, cells, and tissues. One-Sentence SummaryPhotopatterned microgels follow sequences of DNA instructions to transform between complex, meaningful shapes such as letters and numerals.

bioengineering↗

Autonomous untethered microinjectors for gastrointestinal delivery of insulin

The delivery of macromolecular drugs via the gastrointestinal (GI) tract is challenging. Macromolecular drugs display low stability and poor absorption across the intestinal epithelium. While permeation-enhancing drug delivery methods can increase the bioavailability of low molecular weight drugs, the effective delivery of high molecular weight drugs across the tight epithelial cell junctions remains a formidable challenge. Here, we describe autonomous microinjectors that can efficiently penetrate the GI mucosa and deliver insulin systemically. In addition, we performed in vitro studies to characterize insulin release and the penetration capacity of microinjectors and measure in vivo release of insulin in live rats. We found that the microinjectors administered within the luminal GI tract could deliver insulin trans-mucosally to the systemic circulation at similar levels to intravenously administered insulin. Due to their small size, tunability in sizing and dosing, wafer-scale fabrication, and parallel, autonomous operation, we anticipate that these novel microinjectors could significantly advance drug delivery across the GI tract mucosa to the systemic circulation.

bioengineering↗

A novel tubulin binding molecule drives differentiation of acute myeloid leukaemia cells

Acute Myeloid Leukaemia (AML) continues to have a poor prognosis, especially in the elderly. One reason for this is that many treatment regimens are not well tolerated by elderly patients. Much current focus is on the development of therapies that can target specific vulnerabilities of AML while having fewer toxic side effects. However, despite much recent progress in developing better drugs, many patients with AML still die within a year of diagnosis, partly due to the fact that it is difficult to identify therapeutic targets that are effective across multiple AML subtypes. One common factor across AML subtypes is the presence of a block in differentiation. Thus screening for compounds that can overcome this block in genetically diverse AML models should allow for the identification of agents that are not dependent on a specific mutation for their efficacy. Here, we used a phenotypic screen to identify novel compounds that stimulate differentiation in several AML cell lines. Lead compounds were shown to decrease tumour burden and to increase survival in vivo. Using multiple complementary target deconvolution approaches, these compounds were revealed to be anti-mitotic tubulin disruptors that cause differentiation by inducing a G2-M mitotic arrest. Together, these results reveal a novel function for tubulin disruptors in causing differentiation of AML cells.

cancer biology↗