Recipient Organization
SOUTH CAROLINA STATE UNIVERSITY
(N/A)
ORANGEBURG,SC 29117
Performing Department
Engineering Technologies
Non Technical Summary
In South Carolina, African Americans represent 30% of the state's population whereas all other minority groups combined total 1%. SCSU is an HBCU with a 93% African American student population. The broader impacts of this work are closely tied to its goals, which are to advance undergraduate research for underrepresented minorities and women, while promoting teaching, training and learning. The work will largely be performed by research associate and undergraduate students at SCSU, which is an excellent means to build up the science and technology workforce of the future - especially in a state like South Carolina, which aspires to participate in the "knowledge economy" but whose current major industries are tourism, agriculture, and manufacturing. Seminar presentations will be arranged to increase general public awareness, and knowledge about the neurodegenerative diseases. This project includes nurturing of a chemistry culture at SCSU that will include participation at local and national chemistry society meetings (poster and oral presentations), and improvement of the SCSU research infrastructure. Existing ties between SCSU and USC will be strengthened by this collaborative work, and access to and use of state of the art research equipment at USC by SCSU researchers will be expanded further. This work will also provide a highly multidisciplinary environment for students. The creation of cutting edge research opportunities, coupled with extensive mentoring, will create a research environment conductive to attracting underrepresented minorities and women, and to guiding them towards scientific careers and higher education. "The 1890 Research and Extension Program works to build collaborations": Existing ties between SCSU and USC will be strengthened by this collaborative work, and access to and use of state of the art research equipment at USC by SCSU researchers will be expanded further. The creation of cutting edge research opportunities, coupled with extensive mentoring, will create a research environment conductive to attracting underrepresented minorities and women, and to guiding them towards scientific careers and higher education. "The 1890 Evans Allen Research Mission is to build the research development capacity at the University": This project will provide an excellent opportunity for minority students to participate in undergraduate research at SCSU under the guidance of Dr. Mahtab. The creation of cutting edge research opportunities, coupled with extensive mentoring, will create a research environment conductive to attracting underrepresented minorities and women, and to guiding them towards scientific careers and higher education. "The 1890 Cooperative Extension mission is to build the land-grant public service outreach capacity of the University by providing specific educational and effective informational delivery services directly---to communities": Findings from research will be sent as bulletins to the Extension Offices for distribution to their clientele. Seminar presentations will be arranged to educate the public and to increase general awareness, and knowledge about the neurodegenerative diseases.
Animal Health Component
(N/A)
Research Effort Categories
Basic
(N/A)
Applied
(N/A)
Developmental
(N/A)
Goals / Objectives
The goal of this project is to develop nanomaterial based sensors of unusual non-B form DNA structures, with emphasis on DNA sequences that are implicated in human neurodegenerative diseases. Novel methods for the detection of DNA are highly desirable for genetic defect detection. Many, if not most, diseases have their roots in our genes. More than 4,000 diseases are thought to stem from mutated genes inherited from one's mother and/or father. Human neurodegenerative diseases such as Fragile X syndrome, Huntington's disease, Mytonic Dystrophy, and Alzheimer disease, to name a few, has been traced to genetic mutations. A particularly interesting and rapidly expanding area of nanoscience and nanotechnology involves research in which inorganic materials and biological molecules converge. Our work will be focused on developing inorganic nanomaterials as optical probes of disease related non-B DNA conformations, and, on studying how modifications of the surfaces of these nanomaterials affect their functionality for sensing sequence directed DNA structures. The colloidal inorganic nanoparticles of our choice will be cadmium sulfide (CdS). These nanomaterials emit visible light when irradiated, and this photoluminescence is sensitive to the nature and amount of adsorbate bound to the particle surface. The nanoparticles can simulate, in terms of size and surface group, a protein-like surface, with the added benefit of a spectroscopic handle to assess DNA-particle interactions. Ultimately, we may be able to design nanoparticles that bind to specific DNA sequences based on the principles that we discover based on our results. These studies will also provide insight into the physical nature of the DNA wrapping process. Long-term potential applications of this research at the DNA-nanomaterial interface include the development of nanoparticles as optical DNA diagnostics, nanoparticle DNA delivery agents, and a more thorough understanding of the operating parameters for DNA-based nanodevices.
Project Methods
Our nanoparticle of choice will be cadmium sulfide nanoparticles with different surface modifications.The usual method of making CdS nanoclusters (diameter 1-20 nm) is an arrested precipitation reaction, in which a Cd(II) salt and a sulfide source are mixed, usually in aqueous solution, in the presence of a stabilizing agent, which most typically is a polymer. In all these methods the stabilizer defines the dimensions of the reaction space to some extent and thus cluster size. "Activation" of nanoparticles by the subsequent addition of metal nitrate salt at basic pH produces nanoparticles that have a nominal M(II)-OH coat. We will also cap CdS particles with cations other than Cd2+, e.g. K+ as the monovalent, and the more biologically relevant Zn2+, metal ion. We would also cap our CdS particles with peptides to further simulate a protein surface. The surface charge of the peptide-coated CdS nanoparticles can be tuned by pH. The nanoparticles will be characterized by UV-Vis spectroscopy, photoluminescence and transmission electron microscopy. Measurement of the nanoparticle effective charge (zeta potential) is an important new experiment to be performed. To date, more than 12 human genetic diseases including myotonic dystrophy, fragile X syndrome, Huntington disease, several spinocerebellar ataxias, and Friedreich ataxia, have been associated with the expansion of CTG, CGG, or GAA repeats. We are particularly interested in studying the left-handed Z-DNA, the cruciform, the tetraplex, the triplex, and the slipped (hairpin) structure forming DNA sequences. Standard oligonucleotides are commercially available from suppliers such as Midland Certified Reagents, MWG Biotech, or Operon. Methods: Our primary method of assessing DNA binding about our substrates is photoluminescence titration experiments, in which the photoluminescence is from the substrate. Comparison of the relative binding constants of the oligonuclides will give us a better understanding of DNA-nanoparticle interaction. The ability of DNA to flex and fold about a protein is key to the physical understanding of DNA functions. In the proposed work, we shall expand our investigation by:(i)varying the nanoparticles by modifications of the surface with more biologically relevant cations, thiols and peptides; (ii)examining DNA sequences with higher order structures and sequences that are implicated in human diseases; (iii)studying the kinetics of the DNA-nanoparticle interactions. (iv)measureing nanoparticle zeta potential and degree of aggregation upon DNA binding. The nanoparticles may function as new reagents to detect anomalous DNA. The ability of DNA to flex and fold about a protein is key to the physical understanding of DNA functions. The work described in this proposal will lead to a better understanding of how the sequence directed structure and/or flexibility of DNA influence its binding to a protein-sized (inorganic) substrate. These results would be of interest to the inorganic nanoparticle community and to the nucleic acid biophysical chemists. The work will also provide a highly multidisciplinary environment for the students.