Ping Liang, PhD - US grants

Adams 9404992 The study of enzymes isolated from organisms inhabiting unconventional ecosystems has led to the realization that biocatalysis need not be constrained to mild conditions and can be considered at pH's, temperatures, pressures, ionic and solvent environments long though to be destructive to biological systems. However, the intrinsic basis for biological function under such extreme conditions is only starting to be addressed, as are applications for what can be called extremozymes. In addition to expanding the search for novel and interesting enzymes from extreme environments, it is important to bring to bear the current sophistication in the study of protein structure and function. Also, those familiar with potential uses of biocatalysis must become more aware of the opportunities and challenges associated with the identification study of extremozymes. Ultimately, given the information acquired from the study of extremozymes, modification to less stable enzymes to improve their ranges of stability and activity remains a possibility. %%% This workshop will bring together representatives from academia, government and industry to provide a perspective on extremozymes and their place in modern biocatalysis. Contributions will cover both fundamental and applied aspects in an effort to describe exciting developments in progress as well as to identify potential opportunities for the use of biological catalysts under extreme conditions. ***

[unreadable] DESCRIPTION (provided by applicant): [unreadable] Characterization of non-random recurrent chromosomal aberrations have proven to be a useful instrument for identification of genes related to cancers and other genetic diseases and for improving diagnosis and prognosis of certain types of cancer. Current studies on characterization of cytogenetic signatures have been limited to the use of data available as individual clinical cases or as small-scale epidemiologic surveys with a primary focus on individual abnormalities and breakpoints using manual approaches. Due to the limitation on data size and the simplicity of methods, more complex patterns and critical breakpoints have not been revealed. Comprehensive cytogenetic data analyzed with new strategies and methodologies are needed to identify novel cytogenetic signatures for human cancer. [unreadable] [unreadable] The proposed project involves analysis of the unprecedented comprehensive cancer etiologic/cytogenetic data deposited in the Mitelman Database of Chromosomal Aberrations in Cancers using computational approaches. By first establishing a computational algorithm with the capability to decode karyotype data to reveal all cytogenetic changes implied by the simplified cytogenetics nomenclature, and by taking advantage of the first digitally compiled comprehensive data of cancer chromosomal aberrations, the project aims: 1) to attempt to establish cytogenetic signatures for cancers without previously known cytogenetic characteristics; 2) to identify new cytogenetic signatures for cancers with established patterns; and 3) to study relationships among different cancers and general patterns for all human chromosomal aberrations. The data resulting from this project should shed light on the molecular basis of poorly understood cancers, the multistage process of tumorigenesis, and relationships among different cancers, and it may provide a global picture of all cancers at the cytogenetic level. [unreadable] [unreadable]

Part 1: Non-technical Description:<br/>The grant’s main objective is to conduct a basic experimental study to understand the feasibility of using a new class of intelligent materials known as magnetoelectric nanoparticles (MENPs) to create a revolutionary technology for high precision wireless deep brain stimulation. Owing to their quantum-mechanical properties, particularly the magnetoelectric effect, MENPs can serve as nanoscale multimodal hubs capable of combining strengths of different fields, while mitigating their weaknesses, to achieve wireless deep brain stimulation with a sub-mm spatial resolution in real time. To date, such capability has not been made possible by any other stimulation technology. Furthermore, by unlocking such unprecedented technology capabilities, MENPs promise to make significant impacts on two large application areas. First, they will allow to treat neurological disorders and diseases, e.g., Parkinson’s, Autism, Alzheimer’s, Major Depression, and others, as well as deadly brain tumors such as glioblastomas at the molecular level, wirelessly and with control levels never available before. Second, by paving a way to wireless brain-machine interface with a record high spatiotemporal resolution, MENPs will enable a wireless connection between the human and artificial intelligence (AI) with record-high spatial and temporal resolutions, thus allowing to create a powerful tool to understand the computing architecture of the human brain and reciprocally, create leapfrog advances in the state of AI. <br/><br/><br/>Part 2: Technical Description:<br/>Unlike any other nanoparticles known to date, MENPs display a non-zero magnetoelectric effect and thus offer a multimodal functionality to electrically, and wirelessly, stimulate neural activity of selected local regions across the entire brain with the spatial resolution in the sub-millimeter size range in real time. The functionality is multimodal because the magnetoelectric effect allows to simultaneously use a combination of remotely controlled magnetic fields, focused ultrasound waves or near-infrared light to generate a spatiotemporal pattern of the local electric field to achieve the required high precision stimulation. Owing to the hybrid approach (magnetics-ultrasound or magnetics-near-infrared) this multimodal application allows to enhance strengths of any of these field modes alone while mitigating their disadvantages. Integration of magnetic fields with the ultrasound and near-infrared modes will be comparatively studied to understand the pros and cons of these two hybrid approaches. In both cases, the magnetic field will be used to deliver most of the energy required to stimulate neurons, while the ultrasound wave or near-infrared light will be used as the second low-energy field mode to define the selected local stimulation region. The experiments using core-shell MENPs made of lattice-matched magnetostrictive core, e.g., CoFe2O4 (cobalt ferrite) and piezoelectric shell, e.g., BaTiO3 (barium titanite) will include two parts: (1) nanoprobe measurements to quantify the multimodal energy addition effects and tailor the key core-shell MENPs’ properties and (2) in vitro studies using hippocampus neuronal cell cultures to understand the interaction of the multimodal effects due to activation by multiple effects on neuronal firing (measured via Ca++ imaging). In addition, we will study the effects of different MENPs’ compositions and surface functionalization on the wirelessly controlled firing capabilities. The two hybrid modes, (i) magnetics-ultrasound and (ii) magnetics-near-infrared, respectively, will be comparatively studied from the perspectives of the required energy, the spatial resolution, the depth of penetration, and the penetration through the skull and the brain tissue. To achieve the aforementioned goals, the GOALI team is made of four experienced researchers with cross-disciplinary backgrounds including (i) a nanotechnology expert who co-pioneered MENPs for medical applications, (ii) a neuroscientist, (iii) a photonics innovator, and (iv) an industry co-investigator who is an accomplished signal processing expert and a co-pioneer (with the principal investigator) of MENPs.<br/><br/>This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.