Center for Functional Imaging
The student could be assigned to one of a number of jobs:
Chemistry - either organic synthesis of compounds for radiolabeling
Radiochemistry - labeling compounds with short-lived isotopes
Automation - develop devices to work with short lived isotopes
Computer software - develop programs for cyclotron and automation
The student can expect to learn organic chemistry laboratory skills, nuclear medicine - positron emission tomography, and practical applications of nuclear chemistry.
Organic chemistry skills and a chemistry background or mechanical/electrical/computer engineering background are required and useful for this position.
Majors: Chemistry, Physics, Computer Science, Engineering Mentor: James P. O'Neil
Mailing address: MS 55-121
Phone: 510/486-5276
email: JPONEIL@lbl.gov
For more information, you can check out the website for the Center for Functional Imaging
Reposted: 1/18/2007

Radiation Biology
The Blakely Group has a number of research interests and pursuits to which a student could be assigned:
Fundamental molecular and cellular mechanisms of radiation damage and repair, as well as clinically-relevant consequences of radiation exposure have been the primary focus of the group's laboratory research programs. The long-term effects of chronic occupational exposure to relatively low doses of ionizing radiations among radiation workers on Earth or in space travel are not completely known. Basic mechanistic information regarding cell damage from and responses to radiations of various ionization qualities is lacking. They are addressing these issues with separate programs. In addition, they are investigating links between changes in lens physiology with the pathology of Alzheimer's disease and mining the utility of neuron stress responses as biological sensors for the detection of neurotoxins.
Low Dose Radiation Research. The group is investigating the importance of cell-type specificity in dictating cellular bystander communication after low targeted doses of Xrays. Their unique experimental approach includes 'painting' a precise stripe of dose utilizing the unique capabilities of the Microbeam generated at the Berkeley Advanced Light Source (ALS) on two normal human cell lines, mammary epithelial cells and fibroblasts grown on microwell slides. Using fluorescence microscopy on a high-precision-controlled microscope stage and fiducial-marked references, the physical locations of the dose stripes are mapped exactly to the location of the biological responses. Computer-based fluorescent analysis of radiation-induced signals has revealed statistically significant differences in the broadening of the effects of the dose stripes to neighboring unirradiated cells with time after exposure for doses below 10 cGy. This involvement of cells not in the irradiated field represents a radiation-induced bystander effect that can be quantitatively evaluated objectively with thousands of cells along the dose stripe and at increasing distances beyond the irradiated area. Using the Gene array coupled with the quantitative RT-PCR validation approach, we have obtained evidence demonstrating cell-type specificity in the constitutive expression of genes, as well as dose-dependent Xray-induced genes, known to be involved in ATM/ATR damage responsive pathways and cell adhesion family of genes. These data suggest cell-type specificity in mechanisms of cell communication in two-dimensional cultures.
Using their novel differentiating human lens epithelial in vitro model system, coupled with an in vivo rat model system, the group is testing the hypothesis that radiation-induced alterations in molecular signaling in lens cells can result in aberrant differentiation in critical cells, leading ultimately to cataractogenesis, a late radiation effect. Information gathered in this area will be used to identify early relative risk of cataracts from key high-LET radiation components of space travel and the development of biological countermeasures. Future collaborations are in progress with the Radiation Effects Research Foundation, and will allow validation with human cataracts from atomic bomb survivors.
The group is also developing a remote sensitive sensing device that can detect biological and chemical toxic substances. It is a novel bioelectronic device interfacing a matrix of living neurons to a CCD for massively scalable readout of neuronal activity, as a toxin detector and for restorative medicine. The device can ultimately be deployed by remote operating robotics with information transmission by telemetry to a base station.
You can read more about the work at their website:
http://www.lbl.gov/lifesciences/CMB/Blakely.html
Mentors: Eleanor Blakely and Kathy Bjornstad
Mail Stop: 70A-1118
Phone: (510)486-6595
email: EABlakely@lbl.gov; KABjornstad@lbl.gov
Student Research Abstract; Summer, 2005
Posted 12/12/2005

Repair of DNA Damage in Human Cells
DNA damage from environmental sources as well as from the cellular metabolism itself threatens the integrity of the genome if not detected and removed. Moreover, many human genetic diseases that involve defects in DNA repair are associated with severe developmental, neurological and immunological abnormalities and/or symptoms of premature aging as well as frequent cancer predisposition. These facts imply an as-yet poorly understood requirement for DNA repair in normal development in addition to its better documented role in prevention of carcinogenesis. Studies in the Cooper lab are directed toward investigating the possibility that this requirement is related to damage to DNA from reactive oxygen species generated during metabolism, and in particular to lesions that block transcription or replication. Because of qualitative similarity in the lesions induced by ionizing radiation (IR) and by cellular oxidation, understanding the mechanisms for repair of IR damage can contribute to understanding this essential role of DNA repair processes. There is thus expected to be substantial overlap between cellular responses to low dose IR and to endogenously generated oxidative damage.
DNA damage that blocks transcription poses a major threat to cellular viability, and a preferential repair process that rapidly removes lesions from transcribed strands of active genes is an important cellular defense mechanism that is essential for normal postnatal development. The group's major research focus is on elucidating the molecular mechanisms of transcription-coupled repair (TCR) and the processing of oxidative DNA damage in mammalian cells. The emphasis is on characterization of the multiple critical functions of the highly pleiotropic human DNA repair protein XPG, since our evidence suggests that it plays an integrating role in multiple repair processes for DNA damage. The enzymatic activity of XPG is strictly required in nucleotide excision repair (NER) for making the first incision in removal of UV and bulky carcinogen damage, and defects in this function result in the cancer-prone disease xeroderma pigmentosum (XP). We have shown that XPG also plays important non-enzymatic roles both in base excision repair (BER) of oxidative DNA damage through coordination and stimulation of early steps in lesion removal and in TCR -- the preferential repair of lesions on transcribed strands of active genes - through interaction with stalled RNA polymerase, other TCR proteins, and transcription bubbles. Mutations in XPG that inactivate its non-enzymatic functions result in the severe postnatal developmental disorder Cockayne syndrome (CS). One or more of these functions is essential after birth, since mice and humans with knockout or severe truncations of XPG die in very early life, but the molecular basis for this requirement is not clear. They hypothesize that TCR is required for resolving transcriptional encounters with DNA lesions from endogenous sources that increase postnatally, e.g. damage from reactive oxygen species, and that unresolved intermediates in either BER or TCR of oxidative damage are particularly deleterious. However, direct evidence for TCR of oxidative damage is currently lacking, and whether the role of XPG in BER is functionally connected to its role in early steps of TCR remains to be definitively determined. Current studies are directed toward elucidating the molecular mechanisms and cellular regulation involved in TCR and their relationship to repair of oxidative DNA damage. The investigation of protein-protein interactions of XPG has tied the TCR pathway to other important processes for maintaining genomic integrity, including homologous recombination, chromatin assembly, and structure-specific helicase action. The possibility that coordination of these processes is critical for replication in the face of endogenous oxidative damage is of major interest for our future research. In addition, their preliminary evidence suggests that BER of oxidative damage is inducible by low dose IR and requires TCR proteins, and whether this inducible repair process underlies the adaptive response to IR is also of interest.
Approaches used for our DNA repair studies include protein biochemistry and enzymology, molecular biology, cell biology, and structural biology. A studentin this group will work with postdoctoral scientists and research associates in the laboratory to provide assistance with ongoing projects and after initial training will also assume responsibility for the conduct of a well-defined sub-project of his or her own, to be chosen from among a number of possibilities based on the student's interest and experience. Examples include construction of plasmid vectors for recombinant protein expression, protein purification, protein-protein interaction studies, transfection of cultured human cells with expression vectors followed by assays for reporter gene expression, and FACS analysis of particular proteins as a function of the cell cycle in mammalian cells.
The student will gain familiarity with a basic research environment in the molecular life sciences, learn to work as part of an integrated, highly active research team, and be introduced to central current concepts in mammalian molecular and cell biology, particularly with respect to processes necessary for preserving the integrity of the genome. The student will learn mammalian cell culture and will gain knowledge of a wide variety of molecular and biochemical techniques.
A strong background in molecular biology, biochemistry, genetics, or related discipline, together with relevant laboratory experience (which may be course-related) will help a student to be successful in this placement and to take maximum advantage of the research opportunities in the Cooper lab.
Majors: Molecular Biology, Biochemistry, Genetics
Mentor: Priscilla K. Cooper
Mail Stop: 74R0157
Phone: (510)486-7346
email: PKCooper@lbl.gov
Posted: 12/12/2005