Bioengineering

2013 REU Project Descriptions


 Annelise Barron
"Host Defense Peptide Misregulation Involvement in the Etiology of Neurodegeneration"

The Barron lab offers an REU project that relates to elucidating the biophysical mechanisms of neurodegenerative disease. Alzheimer's and Parkinson's disease are both characterized by a slow, neuron-to-neuron transmission of toxic oligomers of anionic peptides such as the ABeta peptide, phosphorylated Tau, or alpha-synuclein. We will investigate the hypothesis that a particular human host defense peptide, the expression of which is stimulated by the acute phase response, can act as an active transporter of these peptide oligomers. There is a strong basis for this hypothesis, which Prof. Barron looks forward to explaining to the REU candidates. Experimental tools to be used will include molecular biophysics, microfluidics, and mammalian cell culture. We will be interacting with collaborators in neuroscience & bioanalytical chemistry.

Responsibilities: Formulation and Characterization of Biophysical Peptide Complexes, Collaboration with Experts in Mammalian Cell Culture.

Desired skills: Meticulous experimental skills and excellent record-keeping, ability to graph and analyze experimental data, analysis and reading of scientific literature.

Positions available: 2


 Kwabena Boahen
"Controlling a Robot Arm with Silicon Neurons"

A fundamental problem limiting the portability of robots today is the amount of energy they consume. Surprisingly, the energy required to control a robot with a computer, a few hundred watts, often equals the actual mechanics. Recent years have seen the development of Neurogrid, a hardware platform that can emulate up to a million spiking neurons while consuming only 5W. Neurogrid presents an unprecedented opportunity to explore the abilities of highly parallel, ultra-low power neural systems in control of a robotic platform. Moreover, understanding what is necessary and sufficient to implement neural controllers could also help us understand the brain's motor controller. Specifically, the student will learn and implement advanced control theory algorithms on a robot arm that is presently being designed by our lab. The student will also have low level access to both Neurogrid and the robotic Neuroarm, and will have an opportunity to learn how the hardware works and even modify it if required.

Responsibility: Student will be responsible for researching and implementing control algorithms for a three degree of freedom robot arm using the Neurogrid hardware platform.

Desired skills: C / C++ programming ability Knowledge of linear algebra Interest in control theory and/or robotics Interest in neuroscience and motor control.

Positions available: 2


Kwabena Boahen
"Making Brain-Like Computers More Practical"

Neuromorphic Computer Architectures use analog silicon neurons to compute, rather than digital logic gates. Networks of these silicon neurons can be configured to perform arbitrary computations by programming their connection strengths, but routing these weighted connections is a very burdensome task. In the Boahen Lab (brainsinsilicon.stanford.edu), we seek to devise more efficient routing schemes by exploiting sparse connectivity and spike-based communication. We are prototyping these schemes on Neurogrid, a custom system developed in our lab with one million analog spiking silicon neurons connected through a digital routing network. An FPGA daughterboard that attaches to Neurogrid routes the spikes generated by the neurons.

There are two related projects available, one software-oriented and the other hardware-oriented. Currently, there is a set of software tools for mapping a desired computation onto Neurogrid's hardware. We would like to improve this software, making the translation from arbitrary algorithm to neuromorphic implementation as automatic as possible. This would be a fun project for a someone who likes programming but doesn't mind dealing with the quirks of hardware, or for someone interested in computation with neural networks. The student could focus on implementing a particular computation on Neurogrid using the existing tools while thinking about how to systematically improve the process of going from algorithm to implementation. The hardware-oriented project would involve optimizing the system's hardware architecture, specifically, the routing operation performed by the FPGA. This would be a good project for someone with a background in computer architecture interested in doing something a little different. The student would implement the enhancement in HDL, modify the driver software, and collect data to show the effect of the enhancement.

Responsibilities/desired skills: For the hardware project, the student will aid in the implementation of an architectural optimization for Neurogrid's FPGA daughterboard. Fluency in VHDL or Verilog is the most important qualification. C++ and Python would also be helpful when modifying driver software. Git/version control experience is a plus. Probablility, algorithms, and linear algebra are also useful. For the software project, the HDL experience isn't necessary, but everything else increases in importance.

Positions available: 2


David Camarillo
"Football Helmet Recognition and Tracking in High Speed Video"

Traumatic brain injury (TBI) has been identified as a major health concern by the U.S. Center for Disease Control and Prevention. Still, the actual mechanism of concussion is unknown, making the injury notoriously difficult and subjective to diagnose. An unbiased and quantitative measure of head kinematics is needed to prevent further injury. With this data, we can correlate concussion likelihood to thresholds and trends in head motion. One such method of measuring head motion is the use of stereo high-definition, high-speed video recordings of helmets during impact. A challenge of measuring helmet motion from video is the need to track points over several frames and from two angles, often manually, to ensure sufficient accuracy and resolution. We are looking for an undergraduate student to develop and implement an algorithm for automatic recognition and tracking of helmet features across several frames. To triangulate these points into 3D space, the algorithm need track the same points in video from both cameras in the stereo configuration. The selection of helmet features will depend on visibility from angles and distribution from one another to provide a better spatial description of the helmet. The end deliverable of a project funded by the 2013 Summer REU Program is software that loads a video, selects helmet fiducial features, and outputs their pixel location over a specified number of frames. These results will be compared to point tracking performed manually, which will provide a baseline of accuracy to be improved upon. The ideal student would start working on this project during Spring quarter for research independent study units and continue through the Summer with REU support.

Responsibility/desired skills: Computer vision (object recognition and tracking), coding experience in any language that can work (preferably MATLAB or C++), interest in the field, and eagerness to learn.

Positions available: 1


David Camarillo
"Laboratory Investigation of Football Helmet Effectiveness at Reducing Head Rotation"

An estimated 1.6 to 3.6 million sports-related concussions are diagnosed in the United States each year, with football accounting for the largest number of cases. Helmets are designed to protect a player's head from injury, but do they really? Conventional wisdom has long linked the incidence of concussion to spikes in linear acceleration of the head, with proposed helmet rating schemes focused on evaluating a helmet's ability to reduce this motion [1]. However, studies have shown that peaks in angular acceleration and angular velocity may correlate better with these injuries [2], suggesting the need to shift the way we design, evaluate, and select a helmet. We are looking for an undergraduate student to assist in a study of a football helmets, and their ability to reduce head angular acceleration and velocity based on data from both in vivo and laboratory experiments. A student funded by the 2013 Summer REU Program will take charge of the latter, designing and executing laboratory experiments that compare how well different helmet models reduce head rotation. Our laboratory is equipped with a variety of head impact apparatus and helmets for the student to use. At the end of the summer, we expect the student to have ranked each of the helmet models based on the results of the laboratory experiments. They will compare these results to a ranking from experiments performed in vivo, and to other rating schemes based on reducing linear acceleration. The ideal student would start working on this project during Spring quarter for research independent study units and continue through the Summer with REU support. References: [1] Rowson, S., & Duma, S. M. (2011). Development of the STAR evaluation system for football helmets: integrating player head impact exposure and risk of concussion. Annals of Biomedical Engineering [2] Rowson, S., Duma, S. M., Beckwith, J. G., Chu, J. J., Greenwald, R. M., Crisco, J. J., Brolinson, P. G., et al. (2012). Rotational head kinematics in football impacts: an injury risk function for concussion. Annals of Biomedical Engineering, 40(1), 1–13. doi:10.1007/s10439-011-0392-4

Responsibilities/desired skills: Experimental design, solid understanding of undergraduate dynamics, MATLAB, interest in the field, and eagerness to learn.

Positions available: 1


David Camarillo
"Miniaturized Polarization Microscope for Embryo Imaging"

Nearly 1 in every 6 couples in the United States experiences infertility, many of whom turn to in vitro fertilization (IVF) to have children. Because IVF success rates are only about 30% per cycle, clinicians often transfer several embryos back to the mother at once in hopes that one will survive and result in a successful pregnancy. However, this often results in twins or higher gestation pregnancies, which carry much higher risks for mothers and children than singleton pregnancies. A major challenge in IVF is to develop a more accurate assessment of embryo viability and choose a single one to transfer back to the mother. In our lab, we have developed a microscope system which can take mechanical measurements of embryos in order to accurately predict viability. We are also working on building a microfluidic chamber to automate the embryo measurement procedure. The REU student working on this project will help to design and build a miniaturized, automated version of this microscope system that can fit entirely inside an incubator in order to avoid placing unnecessary environmental stresses on the embryos. The student will also help integrate a polarization imaging capability into the miniature scope in order to perform mechanical measurements at a consistent location with respect to the meiotic spindle.

Responsibilities/desired skills: Knowledge of optics and microscopy as well as hands-on alignment experience Programming in Labview, Matlab Experience with Solidworks Basic knowledge of electronics.

Positions available: 1


Jennifer Cochran
"Time Course Analysis of Tumor-Associated Receptor Expression Levels in Cancer Models "

The last three decades of research has yielded unprecedented insights into the mechanism of cancer pathogenesis. The dysregulation of cellular signaling pathways mediated by membrane bound receptors has been shown to be an integral part of cancer pathogenesis. For example, several studies have functionally implicated vascular endothelial growth factor receptor 2 (VEGFR2) and αvβ3 integrin in angiogenesis a process which is necessary for the growth of all solid tumors. In addition, a growing body of work supports the hypothesis that because multiple signaling pathways are dysregulated in many cancers, inhibiting a combination of related targets will likely display enhanced efficacy.

Concomitantly, developments in protein engineering have enabled the generation of molecularly targeted therapeutics and imaging agents against these cancers. In 2011, Cochran et al. described an innovative approach to generate protein based therapeutics that simultaneously targeted VEGFR2 and αvβ3 integrin and inhibited angiogenesis in several in vitro assays. The next step in evaluating the potential of these bispecific agents is to examine their ability to inhibit angiogenesis in vivo. A critical issue that needs to be addressed prior to these studies is to ascertain receptor expression levels as a function of time in specific cancer models. This information will enable selection of the most appropriate tumor system as well as the most effective dosage regimen for that model in the subsequent therapy trials.

Aim 1: The student will perform histological screens in tumor xenograft models at various time points to determine the levels of VEGFR2 and αvβ3 integrin that are expressed as a function of time. This aim will elucidate the most suitable model and dosing regimen for therapeutic studies. These experiments will expose the student to techniques involving tissue preparation for microscopy, such as tissue slicing and mounting, antigen retrieval, and incubation with light-sensitive fluorescent probes.

Aim 2: The student will recombinantly express and purify the engineered bispecific proteins in yeast cells and assist with assays to measure their binding and biochemical properties. This aim will offer hands-on experience with protein expression and immunoaffinity purification, both used frequently in protein engineering, and biochemical assays including receptor phosphorylation and cell proliferation. The engineered proteins will subsequently be tested in mouse tumor models for therapeutic efficacy.

Responsibilities/desired skills: Cell culture, histology, immunofluorescence, protein expression and purification.

Positions available: 1


Markus Covert
"Building Whole-cell Computational Models to Predict Phenotype from Genotype"

Our lab is currently working on a computer model of Mycoplasma genitalium which takes every gene into account. Our model tracks all biological processes, including for example DNA replication, RNA transcription and regulation, protein synthesis, metabolism and cell division. Although until now different biological processes have been almost exclusively studied in isolation, they are in fact deeply and inseparably integrated. This whole-cell model will therefore enable us to pursue critically important questions which have never been addressed before.

Responsibilities/desired skills: Under the guidance of PI (Prof. Covert) and together with a team of 3-4 graduate students, the student is expected to participate in network reconstruction, large-scale computational modeling, data visualization and possibly some cell culture and experimentation. Highly motivated individuals with coding experience and a solid background in engineering are desired. Experience or training in biological modeling a plus.

Positions available: 1


Andrew Endy
"Using Negative Genomics to Simplify the Genome of a Small Virus"

Design and construction of synthetic genomes should enable powerful new approaches to the field of bioengineering and biotechnology applications, such as constructing new metabolic pathways in bacteria to synthesize medicines. However, due to the overwhelming complexity of biological systems, most designs to date have largely recapitulated natural sequences. My goal is to pioneer a new method of simplifying synthetic genomes, a process I call 'negative genomics'. I plan to develop this method by systematically identifying and eliminating all cryptic DNA sequences in the genome of the small lytic coliphage phiX174. The intricate architecture of the circular 5.4 kb phiX174 genome encodes 11 gene products via highly overlapped protein coding sequences spanning multiple reading frames. The combination of small size and complexity makes the phiX174 genome an excellent test case for negative genomics. Building synthetic phage genomes has been hampered in the past by the extreme toxicity of these viruses to E. coli. Recently, I developed a method that solves this problem by using yeast as a platform to assemble phiX174 genomes (Jaschke PR, et al. 2012. Virology, in press). Using this method I have decompressed the phiX174 genome (i.e. separated all gene sequences), and showed that the virus is fully functional without gene overlaps. I am now equipped to systematically remove all cryptic gene signatures from phiX174 using negative genomics to generate a simpler and more predictable genome. Specifically, my work could facilitate concise engineering of bacteriophage genomes for improved diagnostics, next generation antimicrobials, and attenuated vaccines. The student will assist me with developing the method of negative genomics by designing new phiX174 genomes in silico, assembling synthetic DNA, and testing the phenotype of these phage genomes.

Responsibilities: Responsibilities of the student include keeping an up to date lab book, designing and performing experiments, maintaining a clean workspace, giving presentations on research progress.

Desired skills: DNA manipulation, PCR, microbiological techniques, and bioinformatics.

Positions available: 1


Kerwyn Huang
"Computational Analysis of Cell Growth and Form"

Recent advances in fluorescence microscopy have driven a revolution in cell biology, revealing molecular mechanisms behind cellular functions. These advances have also revealed the need for quantitative analysis tools to interpret complex datasets. Our lab is developing tools for image analysis and simulated fluorescence microscopy that are broadly utilizable by the cell biology community. The senior thesis project would involve extending and refining these tools, developing GUIs for relevant analysis platforms, and testing these software on a broad range of datasets. The student will learn image analysis skills, and will be involved in links to biophysical models. Student will be mentored by a postdoctoral fellow in the lab. Student will have the opportunity to participate in the writing of manuscripts regarding the method development.
Please contact KC Huang at kchuang@stanford.edu for any further information.
Lab webpage: http:whatislife.stanford.edu

Skills requires: Proficiency in Matlab; experience with GUI design is recommended. Proficiency with C/C++ is recommended but not required. Student should be comfortable with calculus and linear algebra.

Positions available: 2


Craig Levin
"Advanced Molecular Imaging Instrumentation and Alogrithms"

We are constructing advanced clinical and preclinical molecular imaging systems. These cameras are designed to have capabilities beyond that which is currently commercially available. Students interested in working with a team of researchers that are developing instrumentation and algorithms for biomedical imaging should consider a project in the molecular imaging instrumentation laboratory (miil.stanford.edu). Work involves development and integration of sensor, electronics, mechanical, thermal, and software sub-systems as well as steps toward translation of the system into the clinic or into a preclinical research tool.

Responsibilities: Passion for creating a new biomedical imaging system.

Desired skills: Experience with construction of instrumentation, signal processing algorithms, and/or software are desirable.

Positions available: 2


Michael Lin
"Structure-guided Engineering of Bright Far-red Fluorescent Proteins"

Fluorescent proteins are useful models for protein engineering due to our relatively advanced understanding of their structure and function, and their utility in biomedical research. A current important challenge in fluorescent protein engineering is the tuning of excitation wavelengths toward redder wavelengths. Fluorescent proteins have been enormously useful as reporters of gene expression, protein localization, or biochemical activities, but have not been extensively used to for deep-tissue imaging in mammals. This has been due to the fact that natural fluorescent proteins have peak excitation wavelengths in the blue and green regions of the spectrum, wavelengths that are efficiently absorbed by hemoglobin. In this REU project, the undergraduate student will perform structure-guided protein engineering, including mutagenesis, library screening, protein characterization, and fluorescence spectroscopy. The student may also have the opportunity to learn expression and imaging of fluorescent proteins in mammalian cells and mice.

Responsibilities: The student will be joining the project at an advanced stage, and will be responsible for learning and independently performing mutagenesis, screening, and protein characterization including purification, gel electrophoresis, and spectroscopic measurements.

Desired skills: Molecular biology skills and protein characterization experience are preferred.

Positions available: 1


Michael Lin
"Visualization of Protein Synthesis in Subcellular Domains of Neurons Using Microfabricated Culture Devices"

Understanding molecular mechanisms of synaptic plasticity is important to understand how neuronal networks learn and how diseases of learning such as autism or mental retardation develop. The Lin Lab uses a combination of microscopy, microfabrication, and cell culture techniques to investigate the role of protein synthesis in synaptic plasticity with high spatiotemporal resolution and high throughput. We are seeking an engineering undergraduate student to assist in experiments on neurons cultured in microfabricated devices. The student will test the hypothesis that localized stimulation of neuronal synapses results in localized protein synthesis.

Responsibilities: The student will be responsible for PDMS device preparation and neuronal culture. The student will also learn to perform automated fluorescence microscopy and image analysis.

Desired skills: Experience with microfluidic devices, cell culture, and/or microscopy.

Positions available: 1


Norbert Pelc
"Dynamic Attenuator to Reduce Radiation in CT Imaging"

X-ray computed tomography (CT) scans provide immense diagnostic utility to doctors and patients, but also account for half of all manmade exposure to ionizing radiation. In order to reduce the unnecessary radiation from CT scans, we will control and optimize the radiation exposure so that exposure to sensitive organs is minimized while image quality to important regions of interest is maximized. The radiation exposure will be controlled by dynamic motion of a series of metallic wedges. The wedges must be very precisely controlled. An existing proof-of-concept prototype is in place, but in this upcoming we will expand its capabilities for greater stability and reduced imaging errors. The project will involve:

  • mechanical design of the wedge components
  • stabilizing the wedges through design of a frame and housing
  • assembly with motors and controllers to drive the attenuators
  • performing x-ray experiments to validate their performance

The students will work closely with Scott Hsieh, a PhD student leading the effort. In addition, the students will attend weekly group meetings and also meet with Prof. Pelc weekly. They will also work with a senior research associate who is responsible with the lab we will use.

Desired skills: CAD Mechanical design Some experience with motors, circuits and/or robotics preferred but not required.

Positions available: 2


Manu Prakash
"High-throughput Microfluidics for Field Ecology: Tools for Malaria Survillance"

Half the world population is at risk of malaria, a disease that can only spread through a bite of an infected mosquito. 300 -500 million people will get infected this year and ~1 million will not survive this parasite. Human race has fought Malaria for more than 200 years; but our tools for field work have remained unchanged for the last 100 years. We are building new array of low cost tools that can provide automated survillance for where the vectors are and how many of them are infected at a single vector level. The project involves building new tools and testing them in field settings. Interest in mosquito physiology, high-throuput molecular biology techniques and precision instrumentation is a plus.

Desired skills: Thinking and imaging, buliding stuff, getting things done, passion, obesession about what you are passionate about.

Positions available: 2


Manu Prakash
New Model Systems to Study "Origins of Behavior and Multi-cellularity""

Behavior of a living system (organism) is an outcome of its individual biological components interacting in complex patterns. So is it possible to write down a set of equations (in physical terms) that completely describe the behavior of an individual organism and it's interactions with the environment. We are studying primitive fossil organisms (fossil because they should have gotten extinct a long time ago, but did not) that exhibit complex behavior hinting towards origin of multi cellularity in animals. We maintain cultures of these fascinating creatures, an study the biophysics of behavior and decision making in these primitive cells. We make mathematical an physical models describing our data and validate the same.

Desired skills: Passion, phydical biology, microscopy, modeling and culturing techniques.

Positions available: 2


Ingmar Riedel-Kruse
"Mechanical-chemical Coupling During Tissue Morphogenesis Studied with Molecular Force Sensors"
 
The Riedel-Kruse Lab (Bio-Engineering) is fascinated by the emergent dynamics of biological systems, and we focus on two topics: (1) Biophysics of Development and (2) Biotic Games. http://www.stanford.edu/group/riedel-kruse/. This project seeks to understand the coupling between chemical and mechanical signals during animal development. We use FRET based force-sensors to map out the dynamic tension fields during zebrafish morphogenesis. Mathematical modeling aids data interpretation and hypothesis formation.
 
Responsibilities: You will help to deliver molecular FRET based force probes into early zebrafish embryos and then image the subsequent developmental events with the goal to describe the force and tension fields driving these events. Quantitative data analysis and also modeling can be part of the project. Based on interest you can take a more experimental or theoretical approach to the problem.

Desired skills: The skills listed below are what you will likely encounter during the project. We don't expect you to have all these skills before you come this project actually provides a great opportunity to learn and acquire new skills.
  • Molecular biology
  • Imaging
  • Programming image analysis
  • Working with zebrafish and cell-culture
  • Programming data analysis / modeling Strong motivation and curiosity

Positions available: 1


Ingmar Riedel-Kruse
"Remote Experimentation for Online Education, Citizen Science, and Biotic Games"

The Riedel-Kruse Lab (Bio-Engineering) is fascinated by the emergent dynamics of biological systems, and we focus on two topics: (1) Biophysics of Development and (2) Biotic Games. http://www.stanford.edu/group/riedel-kruse/. This project seeks to develop interactive online interfaces and equipment that enable remote users (typically non-scientists) to interact with biological data and even run their own experiments. It is our vision to develop such online interfaces (often structured in game form given the motivational and educational power of games) to enable average citizen to help solving bio-medically relevant research questions ("human computation" / "crowd-sourcing" / "citizen science") and as a medium for large-scale informal and formal science online education.

Responsibilities: You will develop interactive online user interfaces and/or work on hardware development. There is a larger development effort going on in the lab, and we will jointly identify a sub-project that suits your background and interest. For example, your project could focus more on the creative-artistic, the programming, the data analysis aspects, or the device building of our larger effort.

Desired skills: The skills listed below are what you will likely encounter during the project. We don't expect you to have all these skills before you come this project actually provides a great opportunity to learn and acquire new skills.

  • Molecular biology
  • Imaging • Programming image analysis
  • Working with zebrafish and cell-culture
  • Programming data analysis / modeling Strong motivation and curiosity

Positions available: 2

Christina Smolke
"Design, construction, and characterization of metabolite-responsive RNA switches"

RNA is a versatile substrate for programming sensing, processing, and control functions within cells. The Smolke lab has engineered a ribozyme-based switch platform that converts a molecular input signal (ligand concentration) into a programmed cellular response (gene expression). To support rapid generation of RNA switches with specific regulatory activities, the lab has also developed a high-throughput and quantitative in vivo screening strategy, enabling switch activities to be matched to application-specific requirements. This research project will explore the design, construction, and characterization of synthetic RNA switches that are responsive to therapeutic and metabolic targets of interest. The effect of switch design and assembly on regulatory activity is still not well understood. To gain mechanistic insight into switch function, ribozyme-based switch activities can be measured both in vitro through ribozyme cleavage rate and in vivo through gene expression. Results will inform the development of more robust switches that can be implemented for use in targeted molecular therapies and metabolic engineering.

Responsibilities: Researcher will assist with both in vitro techniques (PCR, transcription, reverse transcription, surface plasmon resonance) and in vivo techniques (DNA transformation into bacteria and yeast, flow cytometry, FACS). All experimental training will be provided; however, some previous coursework or research experience in organic chemistry or molecular biology is desired.

Desired skills: All experimental training will be provided; however, some previous coursework or research experience in organic chemistry or molecular biology is desired.

Positions available: 1


Christina Smolke
"The Development of Protein Responsive miRNAs"

Mammalian cell complexity is largely due to the sophisticated control mechanisms modulating the expression of endogenous genes. Various molecules in the cell are organized into networks, which can upregulate and downregulate a myriad of genes in response to both intracellular and extracellular changes. The ability to create synthetic molecular networks that direct novel gene regulation patterns in response to intracellular or environmental signals would greatly advance our cellular engineering capabilities. This project focuses on the development of a ligand-responsive control platform based on microRNAs (miRNAs), which control gene expression using RNAi. These miRNAs are designed to modulate the expression of a gene of interest in response to the levels of disease markers and/or other relevant proteins inside the cell. Initial efforts will use molecular biology techniques to quantitatively characterize the miRNA switch platform. Focus will be placed on understanding and quantifying the relationship between the input (disease marker) and output (expression level of the gene of interest). This information will be used to build a mathematical model which will enable forward engineering of synthetic gene regulation circuits using the miRNA platform.

Responsibilities: Perform experiments in bioengineering, synthetic biology, molecular biology and data analysis. Basic knowledge of molecular biology and calculus is required.

Desired skills: Previous experience with molecular biology techniques such as RT-PCR, cloning and western blot is desired, but not required.

Positions available: 2


Christina Smolke
"Development of RNA Aptamers for Benzylisoquinoline Alkaloidss"

The Smolke lab has developed synthetic in vivo RNA controllers that regulate gene expression in response to several small molecule targets. Small molecules are able to act as input for these controllers due to the inclusion of an aptamer domain. Aptamers are artificially-selected single-stranded oligonucleotides that bind to targets with high affinity and selectivity. Aptamer generation is performed in vitro using the Systematic Evolution of Ligands by EXponential enrichment (SELEX) process. This procedure screens large combinatorial nucleic acid libraries for desired target binding through a series of iterative selection rounds. While RNA controllers have exciting potential to detect, respond to, and control intracellular metabolites in many different living-systems, new aptamers for novel targets must be developed to create novel functional controllers that respond to practical targets. Our laboratory has been working to develop aptamers for metabolites of the benzylisoquinoline alkaloid (BIA) pathway. BIAs are an important class of plant natural products that exhibit diverse pharmacological activities, including anti-HIV, anti-microbial and anti-cancer activities. As these products are nearly impossible to isolate from their native hosts and cannot be chemically synthesized, our lab is constructing this complex pathway in a yeast host to produce and isolate BIAs biosynthetically at large scales. The integration of BIA aptamers into our RNA controllers has the potential to improve our understanding and construction of biosynthetic pathways, in particular for BIA biosynthesis.

Responsibilities:This project will train students in skills associated with synthetic biology, bioengineering, analytical chemistry and data analysis. The researcher will assist with the in vitro selection of RNA aptamers that bind BIA metabolites and be responsible for analyzing and optimizing their binding properties. The development of the RNA aptamers will include experiments involving PCR, agarose gels, HPLC and SPR analysis.

Desired skills: All training will be provided; however, laboratory experience in either analytical chemistry or molecular biology will be an asset.

Positions available: 1


Fan Yang
"Engineering Biomimitic Hydrogels for Understanding Stem Cell-niche Interactions"

Stem cell functions are regulated by local cues present in their microenvironment including soluble growth factors, extracellular matrix (ECM), cell-cell interactions, as well as mechanical signals such as the matrix rigidity. While the effect of individual type of microenvironmental cues on stem cell behavior has been studied in great depth, little is known about how the complex interplay of multiple types of signals would influence stem cell behavior. In this project, the student will work with Prof. Yang and other senior lab members (e.g. postdocs or Ph.D. students) on understanding the effects of interactive signaling on stem cell in 3D using biomimetic hydrogels. Results from such studies would help predict stem cell phenotype in vivo and direct rational design of stem cell niche for tissue engineering applications.

Responsibilities/desired skills:Under the guidance of PI, the student will be responsible for literature search, designing experiment details, carry out experiments and data analysis, and present the progress in both oral and written format. Prior experience in cell culture, biomaterial and/or molecular biology is preferred, but not required.

Positions available: 2


Fan Yang
"Develop Controlled Delivery System to Guide Tissue Regeneration"

Hydrogels are attractive candidates as drug delivery platforms due to their biocompatibility and wide use for tissue engineering applications. Most hydrogel platforms developed so far often lead to burst release of encapsulated drugs such as proteins. However, long-term sustained protein release is desirable for guiding cellular processes and tissue regeneration in situ.The overall goal of this project is to develop a facile strategy for sustained protein release from hydrogels by tuning the hydrogel network structure, homogeneity and degradation.

Responsibilities/desired skills: Under the mentorship of PI, the student will be responsible for literature search, designing experiment details, carrying out experiments and data analyses, as well as presenting progress report in both oral and written format. Prior experience with biomaterials, drug delivery or tissue engineering would be a plus, but not required.

Positions available: 1


 

 


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