The University of Washington Center for Integrated Health of Women, Children and Adolescents (Global WACh) aims to contribute to scientific discoveries, develop and nurture future leaders in science and foster collaborative approaches to improving the health and well-being of women, children and adolescents.
The Coulter Translational Research Partnership Program (Coulter TRP) at the UW is dedicated to improving human healthcare by supporting translational research in biomedical engineering-research directed at the transfer of promising technologies within the university research laboratory that are progressing towards commercial development and clinical practice.
As part of these commitments, Global WACh and Coulter TRP are offering pilot research funds to support collaborative translational research in medical engineering that addresses clinical needs of women, adolescents and children.
Applicants must address unmet clinical needs and must have strong potential for near-term clinical impact and improved healthcare. Potential topics include, but are not limited to:
Innovations that jointly impact women, adolescents and children, and/or approaches that address dual outcomes or benefits, will be prioritized. Proposals that include graduate students or trainees are strongly encouraged. While it is not a requirement, research teams that include new collaborations are strongly encouraged.
Famed global health pioneer Dr. Paul Farmer recently described surgery and anesthesia as “the neglected stepchild[ren] of global health.” 3.5% of the 234 million major surgeries performed in 2008 took place in countries that make up the poorest 35% of the world’s population. Many deaths could be averted by timely surgical care, primarily for pregnancy complications and abdominal conditions, but the cost and inconvenience of providing adequate anesthesia in low resource settings is great.
The project aims to develop a low-cost, portable anesthetic delivery device that can address the shortcomings of current devices by replacing bulky and expensive temperature regulation mechanisms with inexpensive materials. This grant will enable the investigators to prove the concept of our innovation and set the groundwork for an ultra-miniaturized device to be used by minimally trained anesthesia technicians in low-resource settings.
The long-term goal of the project is to develop a point-of-care assay for HIV drug resistance by reducing a complex laboratory process into a rapid and easy-to-use format. The existing laboratory-based oligonucleotide ligation assay (OLA) developed by the Frenkel lab allows highly-specific identification of HIV drug resistance, but the complexity of the process (sample preparation, nucleic acid amplification, ELISA- based detection) has restricted adoption in some low resource labs of the developing world.
As a first goal, the team will simplify each step of the assay – specimen preparation, PCR (nucleic acid amplification and ligation), and target detection – to provide a less complex test for low resource laboratories; these simplifications will be the first steps to developing a point-of-care assay appropriate for use outside the laboratory.
The role of the Lai lab is to develop specimen preparation technologies that can enable nucleic acid target enrichment from a larger whole blood volume in two simple steps, mixing and separation. This approach will provide a great number of viral templates to be submitted to PCR to allow simplifications in the amplification and ligation steps (described below) without losing sensitivity. To date we have designed and synthesized stimuli-responsive polymers that form complexes with oligonucleotides. Next the team will utilize these polymer reagents for isolating DNA from the specimens.
The role of the Frenkel lab in the Coulter/GlobalWACh seed project is to adapt the OLA from two nested rounds of PCR to a single round of PCR and modify the ligase reaction so that it can be performed in the same “tube” (well). The team plans to pursue these advancements using DNA for a test that would be performed prior to ART to detect transmitted resistance, and in a slightly different assay using plasma RNA that would be used in individuals taking ART to detect “virologic failure” and proceed directly to testing for drug resistance. (This latter assay was added after the award of the Coulter WaCH grant.) To date the team has simplified the nested to a single round of PCR using plasma. Next the team will work on proceeding directly to the ligase reaction, and using on applying the single-round PCR to blood DNA isolated by Dr. Lai.
The role of the Lutz lab is to reduce the multi-step laboratory detection process into a rapid and simple strip format that can be read by eye. In the existing assay, detection is based on the enzyme-linked immunosorbent assay (ELISA) with additional stringency wash steps to remove non-target (non-ligated) oligonucleotides, and it requires comparison of two or more target signals detected by an instrument. The team is currently adapting the chemistry and assay steps into a paper strip format that will report colored lines for resistant and non-resistant targets. With the Frenkel lab, the team has produced PCR-amplified and ligated products to be used for testing, and has prepared detection strips that show faint signals for the ligated targets.