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Projects and Mentors

The Clemson REU Program: Nature’s machinery through the prism of physics, biology, chemistry and engineering has mentors in Physics, Chemistry, Materials Science, Bioengineering, Genetics and Biochemistry, and Biology. All the mentors have extensive experience in supervising undergraduate research students. Participants will work in pairs with in a dynamic research team led by two principle investigators to:

      • design and conduct experiments;
      • use modern research equipment;
      • learn applied and theoretical methods;
      • analyze data and draw conclusions;
      • present results in multiple formats;
      • enjoy an engaging, academically stimulating, and highly collaborative interdisciplinary
      • research environment.
  • Project Title: Active matter driven by molecular motor proteins

    Mentors: Dr. Joshua Alper, Physics and Astronomy, and Dr. Olga Kuksenok, Materials Science and Engineering

    Introduction: Engineered active polymer gels have the potential to revolutionize the next generation of smart nano- and micro-devices. Optically, chemically, and thermally responsive synthetic biomimetic active gels show promise in a variety of applications. The cytoskeleton naturally occurring in nearly every eukaryotic cell is essentially an active gel capable of forming structures, changing shape, and driving oscillations. There are multiple studies using kinesin motor proteins and microtubules to make active gels, and some continuum and fluid models have been used to describe their properties. However, these studies only hint of what is possible with biomimetic active gels incorporating motor proteins.

    Research Plan: Two participants will collaborate to study motor protein driven active gels. One participant, primarily engaged in experimental research in the Alper Lab, will reconstitute active polymeric gels using microtubules, crosslinking microtubule associated proteins (Ase1 and inactive motors), and motor proteins (axonemal dyneins). This participant will vary the components, and concentrations of the gel components, to generate gels with a range of active properties. The participant will measure the passive and active properties of the gels using fluorescence microscopy and force spectroscopy (optical tweezers). The other participant, primarily doing theoretical and computational work in the Kuksenok Lab, will model the passive and active properties of these gels. This participant will adapt models developed and validated for chemo-responsive synthetic gels to predict and explain the behaviors of these active biological gels. Together, the participants will design, build, model, and engineer nature’s machinery to generate active gels with novel properties. The participants will make significant contributions to this exciting field of active nano-biological materials by expanding the molecular constituents used in the design of these gels.

    Equipment/techniques participants will learn and use: fluorescence microscope; optical tweezers; general biochemical and biophysical equipment including centrifuges, gel electrophoresis, and spectrophotometers; high performance computer cluster.

  • Project Title: Molecular mechanisms of diseases involving protein-DNA interactions

    Mentors: Dr. Emil Alexov, Physics and Astronomy, and Dr. Weiguo Cao, Genetics and Biochemistry

    Introduction: Solving the molecular mechanisms of human diseases is crucial for developing effective and specific therapeutics. Many of human diseases originate from DNA variants resulting in mutant proteins, however, the molecular mechanism of many of them remain unknown. For example, Rett syndrome (RTT) is a brain disorder associated with severe language, learning, and coordination problems that affects 1 in 10,000 – 15,000 females. Despite of the high occurrence of RTT and the severe outcome, the molecular mechanism of the disease is still unknown. There are at least 841 mutations found in RTT patients, about 25% of which are found in a protein that binds DNA. Similarly, Snyder-Robinson syndrome, which is a genetic disorder associated with intellectual disability, is caused by mutations in spermine synthase, but the molecular mechanism for some of them is still unknown. The participants will identify distinct biophysical phenotypes caused by disease-causing mutations in proteins, leading to insights into the mechanisms of the corresponding diseases.

    Research Plan: Two participants will collaborate to study the mechanisms of proteins involved in the regulation and maintenance of DNA including methylcytosine-binding proteins, DNA repair proteins and spermine synthase. The project will focus on understanding the molecular mechanisms of human diseases linked with mutations in these proteins. One participant, primarily doing molecular biology in the Cao Lab, will generate protein mutations, express mutated genes in E. coli, and purify wild type and mutant proteins. The participant will investigate DNA/protein binding affinity and stability by gel mobility shift analysis and fluorescence anisotropy. The other participant, primarily doing computational work in the Alexov lab, will generate in silico mutations, carry out energy minimizations, and predict the effect of mutations on the binding affinity and stability. The participant will also use molecular dynamics simulations to reveal the effects of mutations on the 3D structure of protein. Together, the students will help to understand the fundamental molecular mechanisms of protein-DNA binding in health and disease.

    Equipment/techniques participants will learn and use: mutagenesis, PCR, DNA sequencing, FPLC, gel electrophoresis, fluorospectrophotometry, absorption spectrophotometry, plate readers, the Information Technology Center (ITC) Data Center, and the “Palmetto cluster” supercomputer.

  • Project Title: The effects of radiation on cells and tissues

    Mentors: Dr. Endre Takacs, Physics and Astronomy, and Dr. Delphine Dean, Bioengineering

    Introduction: High dose radiation treatment is commonly used to kill diseased cells within a target tissue, but healthy cells near to the target are also exposed to low doses of radiation. Preliminary evidence suggests that low levels of radiation has a beneficial effect. However, how various tissues react to low doses of radiation and the underlying physical, chemical, and biological pathways that take place during irradiation remain largely unstudied. The goal of the project is to determine how vascular tissues respond to low dose radiation and whether their responses are wavelength dependent.

    Research Plan: Two participants will collaborate to study the interaction between low levels of monochromatic soft x-ray radiation and biological tissues. One student, primarily working in the Dean Lab on tissue culturing, will grow vascular cells in 3D culture and characterize their properties with various biological assays. The other student, primarily performing medical physics research in the Takacs Lab, will characterize low dose x-rays and use them to irradiate tissues. Together, the participants will precisely characterize radiation that cell cultures receive and use well defined protocols to understand the biological response to understand how low levels of radiation affect individual biological machinery in cells and cell cultures.

    Equipment/techniques participants will learn and use: mini-x-ray tubes, solid-state x-ray detectors, single-photon counters, spectral analysis software, statistical analysis software, cell culturing, optical microscopy and image analysis, cell proliferation and cell cycle analysis, cell function and differentiation assays

  • Project Title: Three-photon absorption probes for deep tissue imaging

    Mentors: Dr. Ramakrishna Podila, Physics and Astronomy, and Dr. Terri Bruce, Biological Sciences

    Introduction: Deep-tissue fluorescence microscopy is currently impractical because the cytotoxicity of high emission probes limits imaging depth to tens of microns in tissue with lower emission biocompatible probes. Development of biocompatible probes that simultaneously absorb three near-infrared photons would improve focusing and prevent auto-fluorescence, enabling deeper tissue imaging.

    Research Plan: Two participants will collaborate to study new three-photon absorption (3PA) probes in deep tissue medical imaging. One participant, primarily doing nanotechnological research in the Podila Lab, will use wet-chemical synthesis to make europium-doped zinc oxide (Eu-ZnO) nanoparticles with high theoretical 3PA coefficients and conjugate glioblastoma tumor-targeting peptides to them. The participant will vary the amount of Eu dopant to optimize emission without compromising strong 3PA and characterize the nanoparticles using spectroscopic tools. The other participant, primarily doing cell biological research in the Bruce Lab, will culture glioblastoma cells for assessing imaging efficiency and macrophages and endothelial cells for evaluating the nanoparticle biocompatibility with healthy non-cancerous cells. This participant will characterize the biocompatibility of the nanoparticles by measuring cellular responses to nanoparticle exposure using cytotoxicity, reactive oxygen species, and ELISA assays to quantify inflammatory cytokines. Together, the participants will explore three-photon imaging as a tool to enhance the study of nature’s machinery. In doing so, participants will address the major limitations of current three-photon imaging technologies by producing biocompatible probes with highly non-linear absorption coefficients, long emission wavelengths, and high quantum yield. Such improvements could enable imaging through up to 3 cm of tissue for non-invasive diagnosis of deep tissue diseases and the study of biological machinery in vivo.

    Equipment/techniques participants will learn and use: Photoluminescence spectrometer, dynamic light scattering, electron microscopy, X-ray photoelectron spectroscopy, non-linear optical Z-scan techniques, multi-photon imaging microscope, mammalian cell culture, ELISA, and LDH cytotoxicity assay

  • Project Title: Fluorescent quenching of organic dye molecules by aromatic amino acids

    Mentors: Dr. Feng Ding, Physics and Astronomy and Dr. Hugo Sanabria, Physics and Astronomy

    Introduction: The quenching of rhodamine and fluorescein dyes by aromatic amino acids tryptophan (Trp), tyrosine (Tyr), Histidine (His), and phenylalanine (Phe), which plays an important role in the study of the conformational dynamics of protein folding. Fluorescence quenching becomes crucial in quantitative fluorescence measurements like Förster Resonance Energy Transfer (FRET). The fluorescent character of organic dyes originate from the presence of a planar, aromatic xanthene core, and the selective quenching of organic dyes is based on the reduction potential of the dye by efficient photoinduced electron transfer (PET) that occur between the first excited singlet state of the dye and the ground-state of Trp, for example. Molecular dynamics simulations on interactions of rhodamine with Trp, show an energy landscape with an energy minimum corresponding to a close-stacked configuration essential for efficient quenching. Fully understanding the structural and energy transfer mechanisms will enable the study of a wide range of biomolecular mechanisms by fluorescence techniques.

    Research Plan: Two students will collaborate to study the quenching of organic dyes by aromatic amino acids and by organic solutions. One student, primarily involved in experimental research in the Sanabria Lab, will perform fluorescence spectroscopic measurements to help elucidate the mechanism of quenching (e.g. static or dynamic quenching) of rhodamine dyes by several amino acids (i.e. Trp, Tyr, His, and Phe). Time resolved fluorescence and spectra will distinguish the difference between static and dynamic quenching. The other student, primarily involved in computational research in the Ding Lab, will perform molecular dynamics (MD) simulations and density functional theory (DFT) calculations to calculate the expected chemical shift in the solution state. The MD studies on dye-amino acid interactions in aqueous solution will provide atomistic insights into fluorescence quenching. In conjunction with classical MD studies, the student will perform discrete molecular dynamics (DMD) simulations to allow simulation of longer time scales and more complex biomolecular systems. Together, the students will compare the fluorescence parameters and molecular dynamics to the experimental data. This project will help in the design and development of emergent fluorescent-based sensors for detection of amino acids.

    Equipment/techniques participants will learn and use: Fluorescence Spectroscopic tools, first principles Density Functional Theory (DFT), Discrete Molecular Dynamics (DMD) and MD simulations.

  • Project Title: Effects of micro-environment mechanics on parasite biology

    Mentors: Dr. William Richardson, Bioengineering and Dr. James Morris, Genetics and Biochemistry

    Introduction: African trypanosomes physically interact with host tissues, both to avoid being dislodged from important niches and while migrating through tissues. While parasite surface molecules are known to play a key role in this interaction, little is known about the consequences of either binding or the mechanical forces applied by host tissues on parasite signaling cascades. While it is clear that the availability of various metabolites participates in the regulation of parasite development in various niches, the role of physical interactions in those compartments on development has not been resolved.

    Research Plan: In this proposal, two participants will collaborate to study the consequences on trypanosomes of physical interactions with the environment. One participant, primarily working with mechanical bioreactors in the Richardson Lab, will test the adhesion affinities and binding strengths between trypanosomes and surfaces with a range of biochemical coatings, substrate stiffnesses, and mechanical deformations.

    Equipment/techniques participants will learn and use: Mechanical bioreactors; surface modification chemistries; molecular and cell biology techniques.