Richard Harland, Professor

Closed (1) Genetic Analysis of the neural development of Xenopus laevis

Closed. This professor is continuing with Spring 2017 apprentices on this project; no new apprentices needed for Fall 2017.

The focus of the lab is to understand development; that is, the molecular mechanisms that orchestrate how a single cell (the egg) forms into an adult animal with a multitude of functioning organs. In particular, this project will focus on genes involved in patterning the developing neural tissue that give rise to the future brain and spinal cord.

Past undergraduates are trained in developmental biology, genetics, and molecular biology. We encourage students as they become more senior in lab to pursue independent projects. As people graduate, and as the projects progress and new experiments are initiated, we are always looking for excellent undergraduates to join our research team.

Qualifications: Undergraduates seeking to apply should be motivated, intelligent, and interested in studying molecular biology especially as it pertains to development and genetics. Ultimately, students will be capable of initiating an independent research project and completing it under the supervision of senior members of the lab. Although previous research experience is valuable, no previous research experience is necessary. Students should be able to devote a 9-12 hours/week to laboratory experiments and discussion.
We prefer to recruit Sophomores or Juniors, with the expectation that they will work towards an honors thesis in their senior year. We also prefer to recruit those who plan to take MCB 140 (Genetics) and MCB C100A , (Biophysical Chemistry: Physical Principles and the Molecules of Life)

General: Cloning in-situ probes and performing in-situ hybridization to visualize potential genes involved in neural patterning.
Specific techniques: Molecular biology methods such as polymerase chain reaction (PCR), and subsequent cloning techniques. As the project progresses additional different methods (i.e. in situ hybridization, microscopy, etc.) might be used to visualize different transcripts.

Day-to-day supervisor for this project: Rachel Kjolby

Qualifications: Strong desire to discover mechanisms of development. Self-motivated. Able to carry out a project to completion independently with supervision available. Skills in molecular biology preferred but not required.

Weekly Hours: 9-12 hrs

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Closed (2) Function of RNA-binding proteins and alternative splicing during frog development.

Closed. This professor is continuing with Spring 2017 apprentices on this project; no new apprentices needed for Fall 2017.

The vertebrate organism consists of several hundred different cell types that all originate from a single cell, the fertilized egg. During embryogenesis individual cells must decide upon which cell fate to differentiate to; a complex process that involve signaling between different cells and execution of intrinsic differentiation programs.

The African clawed frog Xenopus laevis is a major model organism in developmental biology and has been instrumental in identifying numerous critical developmental mechanisms and proteins. Embryonic development in frogs is well understood and powerful molecular and histological techniques have been developed that include targeted protein overexpression and gene knockdown. Recently, these embryological methods have been supplemented with genetic techniques, including targeted mutagenesis, and next generation sequencing, which enable whole transcriptome analysis.

A puzzling feature of animals is that the number of genes encoded in the genomes of simpler creatures (such as flies and worms) is comparable to the number in more complex organisms (mice and humans). How can a constant number of genes encode such an increase in complexity? One explanation is the increased use of alternative pre-mRNA splicing in complex vertebrates, which is rare in worms and flies, but affect most genes in higher vertebrates. Through alternative splicing a single gene can give rise to several different transcripts encoding distinct proteins. Alternative splicing is regulated by RNA-binding proteins that bind to the pre-mRNA and recruit the core spliceosome that catalyze the excision of introns.

In a previous screen we identified a number of RNA-binding proteins that affect frog development when overexpressed. We recently published a study on one of these, fus, where we showed that it is necessary for constitutive splicing of an extensive set of developmental regulatory proteins and for gastrulation. Now, we wish to determine the functions of several of the other proteins we isolated in the screen.

The project will include general molecular methods including cloning and subcloning of genes, and PCR based techniques, in addition to frog handling and raising of tadpoles. After initial training the project may require learning of histological techniques such as antibody stainings and in situ hybridization.

Day-to-day supervisor for this project: Darwin Dichmann

Qualifications: The candidate is required to be enthusiastic about science, able to think analytically, pay strict attention to details, and able to work independently after initial training. A long-term interest is desired so preference will be given to sophomores and juniors with interest in molecular and developmental biology. Skills in molecular biology or other lab experience preferred.

Weekly Hours: more than 12 hrs

Closed (3) Regulation of Wnt-signaling by proton pumps during vertebrate development and human cancer

Closed. This professor is continuing with Spring 2017 apprentices on this project; no new apprentices needed for Fall 2017.

Cells communicate through signaling molecules, which bind to receptors and co-receptors at the membrane of the receiving cell. Receptor activation is then interpreted by the cell and induces a wide range of molecular events, such as protein modification, change in gene expression, cell shape change and reaction to subsequent signals.
One such signaling cascade is the Wnt signaling pathway, which plays important roles during animal development, tissue homeostasis and human disease, e.g. cancer. Only recently, it was shown that the activity of several proton transporters is necessary for the activation of Wnt signaling in vertebrate embryos and human cells.
This project will elucidate the molecular mechanism of these proton pumps within the Wnt signaling pathway and how local changes in pH affect signaling in embryos and cell lines. Changes in local pH and Wnt signaling activity are hallmarks of cancer formation and progression, thus the long term goal of this project is to understand their contribution to cancer formation and facilitate new treatments for patients.
For our research we use genetic, molecular and cell biological tools in frog embryos, mice and human cell lines. This offers a wide range of opportunities to learn techniques and gain insight into cell and developmental biology in an open and helpful environment.

The undergraduate researcher will help with molecular cloning, visualization of gene expression, histochemistry, preparation of tissue sections and genotypeing. Optional (depending on student's previous experiences and interests): Animal handling, embryo manipulation, tissue culture, confocal microscopy and quantitative PCR.

Day-to-day supervisor for this project: Peter Walentek

Qualifications: Candidate(s) should be self-motivated, intellectually engaged, and be able to work independently after initial training. Skills in molecular biology or biochemistry preferred but not required; stronger emphasis will be placed on candidates who are able to think logically/analytically and are scientifically curious.

Weekly Hours: more than 12 hrs

Closed (4) Exploring how tissue mechanics and multicellular dynamics shape tissues during organ formation

Applications for Fall 2017 are now closed for this project.

As the embryo takes shape, organs develop into complex functional systems. For an organ to function optimally it is essential that it take on the right general form. Beyond taking on the right overall tissue shape, organs are comprised of intricate patterns, which organize the functional units of the tissue. These patterns include the cortical folds of the brain, the villi of the intestine, and the branches of the bronchiolar tree of the lung. Organization of these units involves dynamic coordination of the various activities of many cells. An understanding of how these complexities arise during development holds the promise of more targeted tissue repair and more efficient engineering of organs.

I am particularly interested in how groups of cells or tissue layers behave and interact mechanically to build patterns in organs and am currently using the avian skin as a model to understand this phenomenon. Specifically, I am investigating the formation of an array of feathers that forms on the skin of the chick embryo. This pattern, akin to the hair follicles in our skin, is strikingly regular, suggesting a very robust mechanism is at play. I am continuing to pursue the hypothesis that cells of the developing skin stretch and pull the tissue into an array of aggregates that each form a feather. Investigating this hypothesis involves observing the cellular and molecular dynamics of this tissue over time in the embryo as well as manipulating tissues and cells in vitro.

URAP PROJECT PROPOSAL Amy Shyer and Richard Harland (PI)
This apprenticeship will involve assisting in the dissection and preparation of chick embryos, in vitro culture of embryonic issues and cells, sectioning fixed tissues, immunohistochemical staining and gene expression studies, processing and quantification of confocal images.

Day-to-day supervisor for this project: Amy Shyer, Post-Doc

Qualifications: Applicants should be self-motivated and possess good communication skills. An understanding of basic biological phenomena is a plus - although no specific undergraduate course work is required. Much of the work will involve delicate handling of embryos or tissues, so candidates should have some technical dexterity. A long-term interest is desired so preference will be given to sophomores and juniors.

Weekly Hours: to be negotiated