Final Project
My final project is a proposal for a research project investigating the connection between DNA methyltransferase 3A (DNMT3A), HOX9A, and the development of acute myeloid leukemia (AML).
- Full Research Proposal: BIOL 463 Final Project
- Annotated Bibliography
Lay Person Summary
Small molecules called enzymes carry out a wide variety of important processes in the body. One such molecule is DNMT3A, which adds modifications to DNA regulatory regions to prevent genes from being expressed as proteins. This process is called DNA methylation, and it is used to regulate the expression of different genes in the cells of the body.
Studies have shown that DNA methylation patterns are altered in many types of cancer, including acute myeloid leukemia (AML). This is a type of blood cancer in which blood stem cells fail to grow into mature blood cells, leaving immature cells called “blasts” crowding the bone marrow and impairing its function. It is a fast-developing cancer with a five-year survival rate of less than 1 in 4. Mutations in the DNMT3A gene that prevent it from functioning properly has been observed in up to 22% of AML cases, as well as in other types of cancer. DNMT3A is one of the earliest mutations that occurs in AML, which suggests that its dysfunction might predispose cells to leukemia development.
But how does this happen? Few studies have investigated the mechanisms through which defective DNMT3A can affect AML. However, a recent study showed that there may be a link between the DNMT3A mutation and decreased methylation of a group of genes called the homeobox-containing (HOX) genes. One member of this family is HOX9A, . Since decreased methylation of a gene can cause increased expression of the gene’s protein product, it is possible that the dysfunctional DNMT3A protein is unable to methylate the HOXA9 gene, leading to overexpression and AML. This study will investigate this possibility by destoying the DNMT3A gene in blood cells, assessing the methylation levels of the HOXA9 gene, and transplanting the cells into mice to determine their ability to cause leukemia. By developing a better understanding of DNMT3A’s role in leukemia development, it will be possible to identify new targets for therapies to help treat those with AML.
Reflection
The learning objectives that I believe I demonstrated through this assignment are:
- Approach questions, concepts, and facts with curiosity
- Deal positively with frustration, setbacks, and failure – there was a lot of frustration in the process of developing a research question!
- Search the literature and effectively extract relevant information from it
- Integrate new factual and conceptual information into your models/thoughts/ideas
- Communicate information, ideas, and findings clearly and succinctly at a variety of levels – demonstrated through the write-up and the lay person summary
- Develop new questions that can be investigated experimentally
- Construct testable hypotheses based on evidence
- Predict the outcomes of observations, experiments, and correlational studies based on a given hypothesis or model
- Select the most suitable techniques to test a hypothesis
- Evaluate what can and what can’t be concluded from given or predicted data/results