Student Research Proposals In Their Own Words (VBS 1001)

1. Student Research Proposals In Their Own Words (VBS 1001) Patricia Goodman-Mamula1, Sarah Armstrong-Serbus2, Marta Borgeson2, Nicole Andrews2, Michelle Kotlovich2, , Martin Wolf1, and Pamela Skinner1 1. VBS 1001 Instructor, 2. VBS 1001 Student, Veterinary and Biomedical Sciences, University of Minnesota Abstract VBS 1001 is an introductory 4-credit course with no prerequisites. This entry-level course is for anyone interested in biotechnology from any college or unit across the university. The objectives of this course include students achieving a basic understanding of cell biology and biotechnology, and students mastering hands on laboratory exercises using modern molecular biotechnology techniques. A major course focus is to foster creative and synthetic thinking. Student's mastery of concepts is used to synthesize a creative project analogous to an actual written scientific grant proposal. Students work in teams under guidance to develop a research plan using biotechnology to solve a current problem, answer an important question, and/or create something new and useful for society. Students generate their own topics and iteratively develop their projects. The groups present their project both in written and oral form to the class. Project points are awarded by both instructors and students. Three representative projects are shown and described by our students (Poster Authors). The projects were creative and the level of sophistication for each project was quite good. General students are able to create and own such projects. An additional benefit to this exercise was the opportunity for students to demonstrate skill sets such as creativity, critical thinking, and communication, not normally evaluated by standardized testing. • Introduction • Scopolamine is an alkaloid substance from the Nightshade family of plants. Its anticholinergic properties are indicated for conditions such as motion sickness and gastrointestinal discomfort, but at higher doses can cause delirium, hallucinations, and severely impaired judgment. In Colombia, unscrupulous individuals can easily extract scopolamine from any number of local flowers of the genus Brugmansia and the resulting extract, called burundanga, can be slipped into an unsuspecting person’s food or beverage. Within five minutes, the victim loses all willpower and is subject to each and every whim of his attacker, yet he appears to be fully conscious. Scopolamine is the perfect criminal weapon, because the victim’s zombie-like state can facilitate the act of burglary, robbery, rape, kidnapping, or even murder. In fact, approximately half of all poisonings in Bogotà are due to scopolamine, and these poisonings are so commonplace that they hardly ever make the news. • Since the window of time between ingestion and onset of symptoms is quite narrow, we propose to engineer a prophylactic medicine which will protect the user from scopolamine poisoning, which is becoming an epidemic in Colombia. The user would take the prophylactic before going out to dance clubs or pubs, where criminals can easily spike food or drink with burundanga. • Research Strategy • View and understand the acetylcholine receptor binding site to visualize the binding pocket for structure and binding properties. • Create a protein with a binding site that has a higher affinity for scopolamine than acetylcholine to bind within the bloodstream before reaching the blood brain barrier. • Create an administration route (oral, intravenous, intramuscular, inhalant, etc.) that will use the protein as a prophylactic substance. • Conduct clinical trials in mice and human, focusing on efficacy, affinity, prolonged bonding action, and the renal and hepatic elimination routes • Expected outcomes and impacts on society • The project is expected to createa prophylactic protein with a higher affinity for scopolamine. • This protein will bind to the scopolamine and transport it out of the body through renal or hepatic pathways with little to no damage to the tissues. • Lowered crime rate and increased public safety will be the greatest in urban areas where scopolamine use is highest. • Introduction • We propose to : • Utilize gene therapy through recombinant virus vectors, in order to transduce apoptosis and inhibit tumor growth in cancerous cellular lung tissue.   • Modify the adenovirus fiber knobs, and construct a retrovirus envelope allowing for target specificity, integrate the Mere15 polypeptide sequence into the novel adenovirus and retrovirus, and to test the recombinant vectors in vivo on A549 xenograftmice. • Research Strategy • Adenovirus and Retrovirus will be teamed together. • (Specific Aim 1) Modification of viruses. Adenovirus created for cell specific targeted delivery, modification of the adenovirus fiber knob with EpCAMantigen. The retroviral vectors envelope will be modified with EpCAM antibodies, combined with CD55 and CD59 proteins to resist degradation by the complement system. EpCAM antigen is highly expressed on an assortment of adenocarcinomas such as breast, ovary, colon and lung, whereas EpCAM antigen expression is limited in normal tissues. • (Specific Aim 2) Integration of the Mere15 polypeptide sequence into an Adenovirus and Retrovirus. The Mere15 gene is found in the Asiatic hard clam has been found to inhibit adenocarcinoma in A549 cell lines. The Mere15 polypeptide sequence fragment will be integrated into the adenovirus at the multiple fragment cloning site. In the retrovirus vector, the Mere15 polypeptide sequence will be integrated on the opposing side of the internal ribosome entry site. • (Specific Aim 3) Test recombinant vectors. The efficacy of the recombinant vectors containing an EpCAM modified fiber rod and Mere15 sequence for adenovirus and EpCAM combined with CD55, CD59, and Mere15 sequence, will be tested in vivo using the A549 xenograft mice. • Expected outcomes and impacts on society • As with all treatments there are possible side effects. Foreseeable side effects are, the possibility of rejection of this teamed viral vector once introduced, and possible allergic reactions.   • Establishment of a treatment plan allows adenoviral and retroviral vectors to transduce adenocarcinomas will allow for further research in targeting other Adenocarcinomas.  The initialization of this novel teamed viral vector would allow for a new pathway in treating, curing and preventing many Adenocarcinomas.  This would be a phenomenal impact on society and steps towards eradicating cancer. • Introduction • The likelihood of a woman having invasive breast cancer at some point in her lifetime is 1 in 8. Breast cancer is the most common form of cancer-induced death for women around the world. The purpose of our research proposal is to help find a more efficient and improved method for treating breast cancer. When one is diagnosed with breast cancer, options for treatment include: surgery, radiation therapy, chemotherapy, hormone therapy, and targeted therapy. The majority of these come with expensive price tags and harsh side effects. While many methods to attack breast cancer exist, none have the efficiency to treat individuals with invasive and metastatic breast cancer. Our plan is to genetically engineer autologous CD8 T cells to confer specificity to HER2-tumor associated antigen. We find these T-cells specifically intriguing, as its receptor is the sole structure on the lymphocyte’s surface that determines the potential of its antigen-recognition. • Research Strategy • We hypothesize that adoptively transferred autologous HER2 specific CD8+ T lymphocytes will play a significant role in the regression of metastatic HER2 overexpressing breast cancer. • Specific Aim 1: Cloning of mice HER2 specific CD8+ TCRs gene into lentiviral vector • Specific Aim 2: Development of autologous HER2 specific CD8+ T cells • Specific Aim 3: Evaluation of T-cell function and avidity, Ex-vivo Clonal expansion of HER2 specific CD8+ T cells followed by adoptive transfer of HER2 specific CD8+ T cells into the patient • Expected outcomes and impacts on society • Through our immuno-stimulant therapy, we expect to see the regression of metastatic HER2 overexpressing breast cancer. Our study would also potentially initiate other studies with genetic modification on animal models in order to research other types of cancer by targeting different antigens. With our successful therapy, technology will be sparked to advance to keep up with scientific progress. It will also decrease the financial burden on those diagnosed with breast cancer and promote less harmful treatment with milder effects. Scoring Criteria for evaluation • Significance: Does the proposed project address an important problem? Will it change the world as we know it? • Approach: Are the conceptual framework, design, methods, and analyses adequately developed, well integrated, well reasoned, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas? • Innovation: Is the project original and innovative? For example: Does the project challenge existing paradigms; address an innovative hypothesis or critical barrier to progress in a field? Does the project develop or employ novel concepts, approaches, methodologies, tools, or technologies for this area? • Presentation: How well was the project conveyed during the oral presentation? Was there a good use of visuals to convey information? Was each aspect of the proposal presented well? • Safety/Social Impact: Where safety concerns addressed? Was effects of project on society and societies' influence of project addressed? Anp32a protein Grading Rough draft turned in on time (5%) Participate in review process (5%) Average grade of your contributions by others in your group (10%) Average student grade of written proposal and presentation (15%) Average instructor grade of written proposal and presentation (65%) 100 points total