Beckman Scholars' Competition

Beckman Scholars Competition Timeline 2010

To be determined....

Benefits

• Support for two summers and one academic year ($6,000 each summer and $4,000 for AY)
• $ 850/summer for research supplies and travel to scientific meetings
• $ 1,600/academic year for research supplies and travel to scientific meetings

Eligibility

1. University of Arizona sophomore or junior students majoring in one of the biological sciences or chemistry
2. American citizens or Permanent Residents of the US
3. Able and willing to work full time for 10 weeks in two consecutive summers in a Beckman mentor's lab as well as 10 hours/week during the academic year.

Guidelines for Application

Click here to download the application

1. Completed Beckman application cover page with one-page personal statement describing career goals and reasons for applying to be a Beckman Scholar
2. One page description of previous research experience
3. Official transcripts from all institutions of higher education attended
4. Letter of recommendation from math or science professor
5. Three (3) -page proposal: based on the article titled “Nanomedicine Targets Cancer". The question is: Design, in as much detail as possible, a nanotechnology-based therapeutic or test that can be applied in medicine today. Possibilities include “lab-on-a-chip” quantum dot or other previously demonstrated approaches. The test or therapeutic must address a specific cellular malfunction, which may be considered at the level of nucleic acids, proteins or small molecules.
6. Spring 2009 course schedule (indicating times available for interview)
7. List of Mentors in order of preference

The finalists will be interviewed. These students will then interview with and chose one of 15 Beckman faculty mentors with whom to work. The Beckman Scholar will prepare a five page proposal for the plan of work to be done in the lab; these will be reviewed by the selection committee and must be approved before payment of the first stipend check . As a condition of this award the student must agree to work full time for 10 weeks for two summers in the selected Beckman mentor's lab and 10 hours per week during the intervening academic year.

Applications are available electronically (Click here to download the application) or from

Carol Bender, Director
Life Sciences South Building, Room 348
Telephone: 520-621-9348
FAX: 520-621-3709
E-mail: bender@email.arizona.edu

Mentors for Beckman Scholars

Dr. Craig Aspinwall
Investigations of the molecular interactions leading to cellular function (and dysfunction) are of paramount importance for a variety of biological research areas. Cellular function is regulated by an elegant series of chemical interactions between diverse classes of molecules including ions, phospholipids, neurotransmitters, nucleic acids and proteins. Chemical signals from both the intracellular and extracellular environments activate intracellular signaling through a variety of pathways including interaction with cell surface receptors, diffusion or transport across the cellular membrane, and interactions with ion channels.

Dr. Giovanni Bosco
Our goal is to understand the basic rules of how the structure of chromosomes and chromatin are regulated in the Drosophila system.  As we better understand how changes in these structures effect their function it will lead to insights that are fundamental to many critical cellular processes, such as chromosome segregation and genome stability, gene expression and epigenetic gene regulation.

Dr. Matthew Cordes
Proteins are the workhorses of the cell, carrying out a variety of biological activities from signaling to catalysis. The structure or architecture of a protein, also known as its fold, is the scaffold upon which these functions are mounted. It is thought that there are several thousand different types of protein fold in nature, of which many hundreds are known today through the work of structural biologists.

Central to our work is the question of how evolution produced so many distinct protein architectures. There is presently very little experimental evidence germane to this question, as very few mutations have been shown to significantly alter protein structures. However, my work on the Arc repressor protein at MIT has shown that in some cases very simple genetic mutations are capable of radically changing a protein's fold.

We now intend to study the mechanisms by which the evolution of fold actually occurs in nature. Our approach is, first, to identify families of proteins which share a common ancestor but which do not share a common fold. Then, through structural and bioinformatic analysis, to reconstruct the evolutionary process which led to the different structures. We will also use protein design, protein engineering and random mutation experiments to mimic structural evolution in the laboratory.

Dr. John Enemark
Bioinorganic chemistry; Molybdenum-containing enzymes; Electronic structure and spectroscopy; pulsed EPR of metalloproteins.

Dr. Indraneel Ghosh
The central motivation of our research program is to synthesize functionally useful macromolecules at the crossroads of chemistry and biology. Our research currently focuses upon three integrated programs:

i) Selection Methodologies: Targeting Protein Surfaces with Small Proteins, Peptides, and Small Molecules. Targets include kinases, HIV-1 cell-surface proteins, beta-amyloid (Alzheimer's) and growth factors (cancer).

ii) Biosensors: Split-protein Reporter Systems (luciferase, GFP, and lactamase) for Detection of Nucleic Acids, Inhibitors of Protein-Protein Interactions, and Inhibitors of Protein kinases. iii) Peptide-hybrid Materials: Coiled-coil and dendrimer based assemblies; Targetd Quantum dot Based Sensors

Dr. Victor J. Hruby
Our research group is interested in the design, synthesis, analysis, conformations, dynamics and structure-biological activity relationships of biologically active peptides and peptide mimetics with special interests in hormones and neurotransmitters that affect human behavior. We are interested in the rational design of antihormones (inhibitors) based on conformation, in hormone and neurotransmitter receptors, in brain chemistry, in the design and asymmetric synthesis of conformationally constrained amino acids, peptides and peptide mimetics, and in the use of NMR and other physical methods to examine peptide and peptidomimetic conformations. We seek to understand the physical-chemical basis for information transfer for these important molecules in biological systems, and utilize synthetic organic chemistry, structural chemistry, bio-organic chemistry, analytical chemistry, physical chemistry, and biology to examine the relationships of structure to information transduction. Some projects include:

1. Asymmetric synthesis of topographically controlled amino acids and their derivatives and ?-turn mimetics, including the following:
2. Synthesis and conformation-bioactivity relationships of alpha-melanotropin (alpha-MSH) in relation to melanoma cancer, pigmentation, feeding behavior, sexual behavior,  cardiovascular function, renal function, pain, and learning.  We have developed conformationally restricted alpha-MSH analogues with extraordinary in vitro and in vivo biological properties including superpotency, superagonist activity, superantagonist activity and super prolonged activity. Computer assisted modeling is being used for design of new scaffolds and more potent and selective compounds including agonists and antagonists for several new melanocortin receptors.
3. Design and synthesis of conformationally constrained neuropeptides. Conformationally restricted, cyclic, rigid enkephalin, deltorphin, somatostatin, cholecystokinin and dynorphin analogues with high receptor specificity and novel bioactivity profiles are being developed. Using a new design principle we are examining the design of ligands that can treat disease states (e.g. neuropathic pain) by design of ligands with overlapping pharmacophores that can simultaneously interact at different receptor types and with different pharmacologies. The conformational basis for their selectivity is being investigated as are new analogues that will modulate pain, behavior, learning, memory, satiety and other CNS effects, and for treatment of AIDS. This information is used in de novo peptidomimetic design.
4. Conformationally constrained oxytocin and vasopressin agonists and antagonists: conformation-biological activity relationships and peptide mimetic design. Design, synthesis and conformational analysis of peptide analogues that can be used to study premature birth, satiety and behavior.
5. We are designing multimeric ligands that can act as molecular machines that will recognize the surface of cancer cells, but not of normal cells, for use in medical diagnosis of cancer, molecular imaging, and cancer therapeutics.

Dr. Joanna Masel
Dr. Masel is a theoretical or mathematical biologist. She focuses on fields in which data is available and hypotheses are testable. She sometimes work with experimentalists, although she does not do experiments herself. The fields she works in are very diverse. They tend to involve complex systems far from equilibrium, whose emergent properties are not immediately obvious from their component parts.

One question Dr. Masel finds interesting is how the rate of evolution can itself evolve. Systems known as evolutionary capacitors are able to store variation in a latent form, releasing it only when necessary. The yeast prion [PSI+] and the heat shock protein Hsp90 are good examples of such systems. Dr. Masel uses population genetics and bioinformatics to study evolutionary capacitance. For example, she analyzes how specific capacitor systems have evolved in the past, predicts how capacitance properties should evolve in general, and studies how capacitance affects the overall rate of evolution.

Dr. Masel also models networks of transcriptional regulators in order to study the evolutionary properties of canalization (also known as robustness) and genetic assimilation. Robustness that is the product of evolution can have very different properties to robustness that is the product of an engineering process. Complex interacting networks can also act as evolutionary capacitors by concealing and revealing variation.

Another interest is how prions, which lack any DNA or RNA, are able to replicate. The incubation period of prion diseases is incredibly precise, leading to high quality in vivo data. Dr. Masel develops mathematical models of prion replication and compares them to data on prion incubation times. This allows her to study how prions replicate and how best to interfere with this replication.

Dr. Katrina Miranda
Nitric oxide (NO), which is synthesized in the body via enzymatic oxidation of L-arginine, is critical to numerous physiological functions but also can contribute to the severity of diseases such as cancer or pathophysiological conditions such as stroke. This diversity in the responses to NO biosynthesis is a reflection of the diverse chemistry of NO. For instance NO can alter the function of enzymes by binding to metal centers. This type of interaction could result in outcomes as disparate as control of blood pressure or death of an invading bacterium. NO can also be readily converted to higher nitrogen oxides such as N2O3 or ONOOH, which have discrete chemical and biological properties. The ultimate result will depend upon numerous factors, particularly the location and concentration of NO produced. Therefore, site-specific modulation of NO concentration offers intriguing therapeutic possibilities for an expanding list of diseases, including cancer, heart failure and stroke.

As a whole, I am interested in elucidating the fundamental molecular redox chemistry of NO and in developing compounds to deliver or scavenge NO and other nitrogen oxides. These projects are designed to answer questions of potential medical importance through a multi-disciplinary approach, including analytical, synthetic, inorganic and biochemical techniques. 

The project categories include:

1. development and utilization of analytical techniques for detection and measurement of NO and other nitrogen oxides as well as the resultant chemistry of these species
2. synthesis of potential donors or scavengers of NO and other nitrogen oxides
3. chemical characterization of these compounds (spectroscopic features, kinetics, mechanisms and profiles of nitrogen oxide release, etc.)
4. biological characterization of these compounds (assay of effects on biological compounds, mechanisms and pathways, in vitro determination of potential for therapeutic utility, etc.)
5. identification of potential targets, such as enzymes, for treatment of disease through exposure to nitrogen oxide donors

Dr. Oliver Monti
Current fossil fuel consumption for energy generation poses a severe challenge to the global climate. Based on foreseeable population and GDP growth. CO2 levels may at least double in the next 40 years, with severe repercussions for the global climate. Any attempt to reduce dependence on fossil fuels must include solar energy conversion as a major component. Research in LabMonti focuses on obtaining a detailed understanding of interfacial processes in organic photovoltaic cells.  Our research seeks to elucidate the chemistry and physics of carriers in organic semiconductors at interfaces on the short length- and time-scales present in organic photovoltaic cells. These cells may offer an attractive low-cost path towards large-scale solar energy conversion.

Dr. Michael Nachman
Michael Nachman and the members of his lab study population, evolutionary, and ecological genetics and genomics. Most work is on mammals with particular emphasis on mice and humans. Research is focused on understanding the forces that shape genetic variation in natural populations. A first major area of research is aimed at uncovering the extent to which natural selection can be detected in patterns of DNA sequence variation, and in particular, in understanding the joint effects of selection and recombination in determining the distribution of genetic variation. A second area of interest is the genetics of speciation. This includes studies to understand the origin and consequences of specific mutations that may limit gene flow between populations and closely related species. A third main area of interest is ecological genetics, aimed at uncovering the genetic basis of traits that are known to be important ecologically. This includes studies on the genetic basis of adaptive melanism in mice.

Dr. Jeanne Pemberton
The surfaces of solids and the interfacial regions between phases are sites of critical importance in an array of relevant processes and technologies. The catalysis of chemical reactions by metals, the corrosion of metals, the pollution of groundwater by toxic chemicals released from soil surfaces, the organization of surfactants at liquid-liquid interfaces important in phase-transfer catalysis, and the conversion of chlorofluorocarbons to reactive chlorine species which destroy ozone in the upper atmosphere are all examples of important chemical processes which occur at surfaces or within interfaces.  Despite decades of intense study, our understanding of the chemistry of these and similar interfacial and surface processes  at the molecular level is still poorly developed. Thus, the development of adequate tools with which to study surface and  interfacial chemistry and elucidation of the molecular details of such complex chemistry represent two of the most exciting frontiers of modern measurement science.

Our research seeks to develop an understanding of such chemistry in several technologically important areas including electrochemistry and electrochemically-related devices, chromatography, self-assembled monolayers, surfactant systems, and environmental and atmospheric systems. Methodologies employed for these efforts include surface vibrational spectroscopies, near-field optical methods, electrochemistry, x-ray photoelectron spectroscopy, Auger electron spectroscopy, LEED, work function measurements, ellipsometry, electron microscopy, and the scanning probe microscopies AFM and STM. Molecular nanoscale imaging figures prominently in our ability to elucidate structural and mechanistic details of surface and interfacial chemistry.

Two images of transient intermediate states on NaCl in its reaction with the mineral acids HNO3 (image above: "strings") and H2SO4 (image below: "peaks") are shown below. These transient structures are formed en route to the final surface products of crystalline NaNO3 and NaHSO4, respectively.

Specific interfacial systems of interest include electrochemical battery and electroluminescent and electrochromic devices, models of these devices fabricated and studied in ultrahigh vacuum, organized molecular assemblies at solid surfaces or air-water interfaces formed spontaneously or by self-assembly or Langmuir-Blodgett techniques, chromatography stationary phase systems, soil and mineral systems important in the fate and transport of environmentally important chemicals, and surfaces such as ice, mineral acids, and alkali halides important in atmospheric processes.

Dr. Joyce Schroeder
Our research interests lie in the area of breast cancer progression and invasion. We use transgenic mouse models of spontaneous carcinoma to understand the molecular mechanisms of primary tumor development and metastatic progression. Tumor growth and invasion is a complex process involving not only the transformed cells of the primary tumor, but also contributions from blood and lymph vessels, extracellular matrix components, cells in the surrounding tissues which provide growth factors, and distant organs which provide hormones. All these contributing factors require the use of animal models to accurately recapitulate tumor formation and spread so that we can properly investigate the molecular mechanisms of cancer.

We are specifically interested in understanding the interactions between the erbB family of transmembrane receptors and other proteins that may modulate their function in neoplasia. Our work focuses on investigating the interactions between the erbB and Wnt signaling cascades, as well as interactions between EGFR (erbB1) and the tumor antigen, MUC1. To fully understand the molecular changes that occur in cancer, our research also focuses on these molecules as they affect the development and function of the normal mammary gland. Through the elucidation of these molecular pathways as they effect breast cancer development, we can expand our understanding of the basic biology of the disease as well as work towards developing effective treatments.

Dr. Frans Tax
My main interest is in understanding how extracellular signals are perceived by plant cells to produce cellular responses. Intercellular signaling is important throughout plant growth and development, but the molecular mechanisms and components of many cellular interactions are still poorly understood. These studies have been hindered by the difficulty in manipulating plant cells with their surrounding cell wall. The results of forward genetic screens have not identified many components, especially receptors, of plant signaling pathways. Our studies are carried out using Arabidopsis thaliana because of the availability of genetic and genomics tools. For example, we have learned from the results of the Arabidopsis sequencing project that this plant genome differs in important ways from the animal and fungal genomes that have been sequenced so far. Gene families are significantly larger in the plant genomes, implying there is greater overlapping function between members of these gene families.

One type of receptor used by plant cells to perceive signals is called a receptor kinase; these are composed of an extracellular domain, a transmembrane domain, and a cytoplasmic kinase domain. Two known ligands for receptor kinases include steroids and small peptides. Receptor kinases are the largest gene family within the Arabidopsis genome (420 genes), and little is known about the function of more than 400 of these genes. To learn more about these genes, we are involved in a project to identify insertion mutants in as many receptor kinase genes as possible (http://plantsp.sdsc.edu). These insertion or knockout mutants will help us determine function even with partial redundancy by allowing us to make selected double and multiple mutants. Morphological analyses of phenotypes of single and multiple mutant strains will define the signaling events involving these specific receptor kinases.

One of our goals is to define the signal transduction pathway for the plant steroid hormone brassinosteroids. Brassinosterods are required for cell expansion, and mutations in genes required for brassinosteroid biosynthesis or signaling have a characteristic dwarf phenotype. A receptor kinase known as BRI1 (brassinosteroid insensitive-1, for the insensitive response of bri1 mutants to the plant steroid hormone brassinosteroids) has been demonstrated to be a plasma-membrane receptor for brassinosteroids. We are using the genetic tools available in Arabidopsis to identify additional components of the signaling pathway that initiates with perception at the plasma membrane and ends with changes in transcription and reorganization of the cytoskeleton.

Dr. F. Ann Walker
We have a wide range of projects available, all of which fall under the general theme of gaining a better understanding of the heme centers in heme proteins that are vital to the life of almost all living organisms. The overall goals of this research are:

1. To evaluate the factors that affect the spectroscopic properties of the cytochromes, including heme substituents, heme reduction level, the nature of the axial ligands, and axial ligand plane orientation. Both synthetic model hemes and appropriate heme proteins, including cytochrome b5 and its axial ligand mutants, are being investigated. Experimental approaches include the synthesis of specially designed model hemes or creation by site-directed mutagenesis and isolation of new proteins with modified heme binding sites, optical, photoelectron, vibrational, NMR, EPR, ESEEM, Mössbauer and MCD spectroscopies, electrochemistry, x-ray crystallography, theoretical calculations and molecular modelling using computer graphics.
2. To characterize the nitrosylheme proteins from blood-sucking insects and simulate their behavior with simpler model hemes. Nitric oxide has been shown to be an important neurotransmitter, among its other important roles as a chemical messenger. We have recently shown that Rhodnius prolixus (the "kissing bug")1,2 and Cimex lectularius (the bedbug)3 each have at least one NO-carrying heme protein in their saliva that apparently helps them succeed in their goal of living on the blood of higher animals. In collaboration with the research group Dr. William Montfort, Dept. of Biochemistry, we are investigating the 3-D structures, spectroscopy (NMR, EPR, UV-vis, MCD, Mössbauer and resonance Raman), thermodynamics (kinetics and equilibria of NO binding, and reduction potentials in the absence and presence of NO) of the NO-binding proteins of Rhodnius prolixus. Current research on these proteins includes preparation and investigation of appropriate site-directed mutants to test hypotheses as to which amino acid side chains affect NO and histamine binding and release.
3. To investigate model hemes and heme proteins by multidimensional NMR spectroscopy. The goal of these studies is to use (and to further develop) modern NMR techniques, such as COSY, NOESY, TOCSY, ROESY, HOESY, HMQC, HMBC, etc., to determine the solution structures and investigate the dynamic reactions (including axial ligand rotation and ligand exchange) of selected model heme complexes in which the oxidation state of iron ranges from Fe(I) to Fe(IV), all of which have relevance to the biological roles of hemes and heme proteins. Computer modelling of the structural and dynamic features will continue to complement the NMR studies.

Dr. Daniela Zarnescu
Our long-term research interests lie in elucidating the molecular basis for cell polarity and how cellular asymmetry controls diverse processes ranging from neural development and synapse remodelling to cell division, growth and differentiation. To address these significant biological questions we are using a combination of genetic, cell biological and biochemical approaches in Drosophila melanogaster and various cell culture models. The following research projects are currently being pursued in the lab:

1. mRNA transport in neural development and disease. Fragile X syndrome (FraX) is the most common form of inherited mental retardation and is due to loss of function for the FMR1 gene, which encodes an RNA-binding protein (FMRP). FMRP is thought to function in neurons by controlling the transport and local translation of target mRNAs, however its requirement for the localization of target mRNAs has remained elusive. To test the role of FMRP in mRNA transport, we have developed a genetically encoded mRNA imaging system with which we can track mRNA live in cultured neurons. These experiments demonstrate that FMRP acts as a regulator of transport for mRNA granules in developing neurons and suggest that defects in transport may contribute to FraX. Future directions include in vivo studies of mRNA transport in neurons and the role of mRNA targeting in normal development and disease. 
2. Novel genes involved in the Fragile X pathway. We recently conducted a dominant modifier genetic screen in Drosophila to identify novel genes that interact with the fly FMR1 (dFmr1) during development and found, among others, 19 alleles of lgl, a tumor suppressor known to control cell polarity. Through a combined genetic and molecular approach we found that Lgl functions upstream of FMRP to control neural development in flies. In addition, Lgl and FMRP form a complex, which contains mRNA and is conserved in mammals. These data suggest a model whereby Lgl controls the localization of FMRP/mRNA complexes in neurons and we are currently testing this possibility. Future experiments will address the molecular mechanisms underlying Lgl function in controlling the distribution of RNA granules in developing neurons. In addition, other genes identified in the screen are currently being mapped and further characterized.
3. Fragile X and stem cells. We are investigating the role of FMRP in neural stem cells using larval neuroblasts as a model system and have preliminary evidence that FMRP may control stem cell proliferation and differentiation. Current experiments include a combination of immunostaining for cell cycle and cell fate markers in conjunction with flow cytometry as well as clonal analyses in the brain to dissect the precise role of FMRP in stem cells. In the future, we aim to identify the mRNA targets which mediate the function(s) of FMRP in stem cells.
4. Fragile X proteins in heart development. We have recently started a collaboration with Dr. Gregorio’s laboratory to determine the possible role of translational control in cultured cardiomyocytes under normal conditions and under stress.
5. Lgl in neural development. We identified Lgl as a novel interactor of Fragile X protein using forward genetics. Currently, we are investigating the role of Lgl in neurons,  a function previously confounded by its requirement in early development. Experiments are being conducted to determine the mechanisms of Lgl function in neural and synaptic development.
6. Lgl – mechanisms for tumor suppression. Lgl is a tumor suppressor in flies and some evidence suggests that it may be required for cancer progression in humans. To test if human Lgl (Hugl1) may be involved in human cancers, we knocked down Hugl1 in a colon cancer cell line and are currently performing in vitro invasion assays as well as animal experiments to test if loss of Hugl1 function results in increased metastasis. Future experiments will focus on identifying the molecular mechanisms by which Lgl contributes to tumorigenesis using a combination of fly genetics and cancer cell models.

 Please list in order of preference, the name(s) of the mentors with whom you would most like to work:

 

Deadline for Application: To be determined.