1994 — 1995 |
Qian, Haohua |
F32Activity Code Description: To provide postdoctoral research training to individuals to broaden their scientific background and extend their potential for research in specified health-related areas. |
Gaba C Receptor Genes in the White Perch Retina |
0.957 |
1998 — 2001 |
Qian, Haohua |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Properties of Gaba C Receptors On Retinal Neurons @ University of Illinois At Chicago
DESCRIPTION (Adapted from applicant's abstract): The application proposes to examine the physiology, pharmacology and kinetics of GABAc receptors on retinal neurons and GABA-rho subunits expressed in Xenopus oocytes. In the first specific aim, the applicant will investigate the five subunits of GABA-rho, which he has cloned from white perch retina. He will examine their electrophysiological and pharmacological properties. He plans to compare the GABA dose-response curves among the five subunits and the pharmacology of antagonists such as I4AA and picrotoxin. In the different subunits, the applicant proposes to compare the kinetics of both the onset and offset of the GABA response using outside-out patch recordings extracted from oocytes. After deciphering these biophysical properties of the individual subunits, he plans to study GABAc receptors expressed in white perch retinal neurons. There will be particular emphasis on bipolar cells and the sensitivity and pharmacology of these cells will be compared to H4 horizontal cells. The applicant will also localize various subunits of the GABAc receptor in white perch retina using in situ hybridization and RT-PCR techniques. The rationale is that a different mix of GABAc receptor subunits in each type of neuron may produce distinct response properties. In a second specific aim, the applicant proposes to study the molecular structure of the GABAc receptor. The rationale is that although the GABAc receptor subunits seem similar to each other, the pharmacology and kinetics are different. Since the amino acid sequence of the subunits are very similar, it may be possible to identify just a few amino acids that account for these differences. The applicant will use site-directed mutagenesis and construction of chimeras to investigate structure/function relationships among these subunits. In the third and final specific aim, the applicant will investigate the modulation of GABAc receptors by second messengers. Based on sequencing data, the applicant has identified cAMP-dependent protein kinase (PKA), protein kinase C (PKC), and calmodulin (CaM)-II kinase consensus sites on the putative cytoplasmic domain of all of these receptor subunits. He will, therefore, investigate the role of phosphorylation in the modulation of each of the five subunits.
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2002 — 2005 |
Qian, Haohua |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Properties of Gabac Receptors On Retinal Neurons @ University of Illinois At Chicago
[unreadable] DESCRIPTION (provided by applicant): GABAergic transmission is an integral part of retinal signal processing, and has been implicated in such functions as directional sensitivity, center-surround receptive field, and color opponency. Dysfunction of GABA neurotransmission has also been implicated in a broad range of neural disorders. Three types of GABA receptors (GABA-A, GABA-B and GABA-C) have been identified. The GABA-C receptors are present prominently in the retina, and exhibit unique properties that are well suited for retinal signal processing. The genes of GABA-C receptor subunits have been located in a locus where several hereditary retinal diseases are linked. The long-term goals of the proposed research are to understand the molecular structure and physiological function of the GABA-C receptors present on diverse retinal neurons. In this proposal, combined electrophysiological, molecular biological and biochemical approaches will be used to study the subunit composition, receptor clustering and biophysical properties of the GABA-C receptors. In particular, we hypothesize that the native GABA-C receptors are formed by co-assembly of gamma2 with multiple rho subunits. The assembly mechanism of these heterooligomeric receptors will be investigated, and the participation of gamma2 subunit in forming the native GABA-C receptors will be examined by antisense oligonucleotide techniques and by immunoprecipitation experiments. In addition, receptor clustering and anchoring are essential for normal signal transmission in neurons. The intracellular proteins interacting with GABA-C receptors will be identified by yeast two-hybrid screening techniques, and their function in modulating GABA-C receptor activities will be examined. Furthermore, the pharmacological and biophysical properties of the GABA-C receptors will be determined both in expression systems and in retinal neurons. These experiments will provide insights into the subunit composition and diversity of native GABA-C receptors. Our studies will help to reveal how GABA-C receptors on retinal neurons are assembled and placed on the plasma membrane, and how the activities of these receptors are dynamically regulated. The information gained from these studies will enhance our knowledge about the physiological function of the GABA-C receptor in the retina, and broaden our understanding of retinal signal processing mechanisms.
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2003 — 2007 |
Qian, Haohua |
P30Activity Code Description: To support shared resources and facilities for categorical research by a number of investigators from different disciplines who provide a multidisciplinary approach to a joint research effort or from the same discipline who focus on a common research problem. The core grant is integrated with the center's component projects or program projects, though funded independently from them. This support, by providing more accessible resources, is expected to assure a greater productivity than from the separate projects and program projects. |
Core--Molecular Biology and Biochemistry @ University of Illinois At Chicago |
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2009 — 2015 |
Malchow, Robert [⬀] Qian, Haohua |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Collaborative Research: the Role of Extracellular H+ in Processing Visual Signals @ University of Illinois At Chicago
Inhibition of neuronal signals is an essential component of the normal processing of information that takes place in the nervous system. Lateral inhibition is a key type of inhibition that is believed to play an especially important role in enabling neuronal computations that mediate visual, tactile, auditory, and olfactory sensation. The experiments undertaken here are designed to clarify the molecular mechanisms of lateral inhibition in the vertebrate retina. The focus of the work is specifically on the role that hydrogen ions (H+) might play in the outermost synaptic connections of the retina and the potential involvement of H+ in lateral inhibition. H+-selective self-referencing sensors and fluorescence imaging studies will be used to examine the molecular mechanisms governing the efflux and influx of H+ from cells in the outer retina, and the effects of neurotransmitters and neuromodulators on H+ efflux and influx will be investigated. This work is structured as a collaborative endeavor between a faculty member and undergraduate students at a strictly undergraduate institution (Indiana Wesleyan University) with two faculty and their undergraduate and graduate students at a Ph.D. granting institution (the University of Illinois at Chicago). It is designed to be one in which undergraduate students truly participate in the research endeavor and become actively engaged in addressing important questions in neurobiology. Undergraduate involvement will be incorporated at both campuses and will include joint video-conference lab meetings and seminar sessions to integrate the undergraduates tightly into the research program. The PI at IWU and several undergraduate students will also travel to spend one month working jointly in the laboratories at UIC. These collaborative studies will serve to better elucidate the role of H+ in synaptic processing in the retina and central nervous system, while catalyzing undergraduate student understanding of and involvement in neuroscience research.
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2009 — 2017 |
Troy, John (co-PI) [⬀] Pepperberg, David (co-PI) [⬀] Shippy, Scott (co-PI) [⬀] Qian, Haohua Saggere, Laxman [⬀] |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Efri-Bsba: Nanoactuation and Sensing of Neural Function For Engineering Future Biomimetic Retinal Implants and Therapies @ University of Illinois At Chicago
ABSTRACT for EFRI-BSBA: Nanoactuation and Sensing of Neural Function for Engineering Future Biomimetic Retinal Implants and Therapies PI: Laxman Saggere, Mechanical and Industrial Engineering, University of Illinois at Chicago (UIC)
Intellectual Merit
Retinal degenerative diseases such as age-related macular degeneration (AMD) affect over 10 million people in the US alone, causing a significant decline in the quality of their lives. Currently available therapies are at best only somewhat effective. Over the last two decades, several groups around the world have been pursuing the development of a retinal prosthesis, with the goal of providing a restorative aid for patients affected by retinal diseases due to photoreceptor degeneration. Nearly all of the current retinal prosthesis developments rely on the principle of stimulating the retina electrically, which is conceptually simple; however, a number of challenges still remain to be overcome in this approach and fully functional, long-lasting devices are not on the immediate horizon. On the other hand, a widely occurring mechanism of intercellular communication in the normally functioning retina as well as elsewhere in the nervous system is the chemical synapse. Inspired by the nature's complex mechanism of transducing visual information into chemical signals via the chemical synapse, the applicants envision an unconventional, but rational, approach to restore the lost functionality of photoreceptors: a light modulated chemical interface at the retina.
Toward this long-term vision of a chemically based retinal implant, the proposed project seeks to understand how the retina and retinal neurons respond physiologically to controlled focal presentation of chemical stimuli in vitro so that a general engineering framework for developing a prosthetic system based on the functionality of the diseased neurons can be further explored. There exist two distinct classes of chemicals, viz. native neurotransmitters and tethered synthetic biomolecules, that are promising as transmitters, and each offers certain unique advantages. Therefore, in this project, they propose to investigate the efficacy and feasibility of eliciting physiological responses of retinal neurons when focally stimulated by both types of chemicals delivered by means of specially engineered micro- and nanoscale delivery devices.
This novel approach is fundamentally different from the more common approach of electrically stimulating retinal neurons, and distinct from chemical-based strategies recently proposed by other groups. Thus, the main intellectual merit of this proposal lies in generating new scientific and technical knowledge that could be transformative to the development of a biomimetic retinal implant to restore lost or damaged retinal function. Ultimately, if successful, this research could lead to a new paradigm and breakthroughs in retinal prostheses.
Broader Impacts
The proposed project, if successful, could break new ground in the area of visual prosthesis and someday help provide vision perception to millions of people affected by retinal degenerative diseases. The devastating complications associated with vision loss, and the progressive aging of the US population with a corresponding increased incidence of AMD in otherwise healthy individuals, emphasize an urgent national need to develop effective prostheses and therapies for retinal degenerative diseases. Beyond the impact on vision health, this research could also lead to other novel drug delivery strategies and biomimetic therapies for treating a variety of neurological disorders such as Parkinson's.
The interdisciplinary collaboration of researchers with a diverse expertise in this project provides a unique opportunity and framework for interdisciplinary education and training of secondary school through postdoctoral students at the frontiers of engineering, neuroscience, and medicine. Four graduate students and one postdoctoral student will undertake interdisciplinary research addressing the tasks involved in this project in the investigators' labs across three different colleges at UIC. Several educational activities integrated with the proposed research including undergraduate research and outreach will be implemented.
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