Promoting diversity through sub-cellular mass spectrometry discoveries: metabolic encoding of the embryonic body plan

This project is designed to enhance the diversity of the biomedical research workforce. A PhD Graduate Student from underrepresented backgrounds will be trained to enable their original research and career development at the frontiers of chemistry and biology. The trainee will learn advanced bioanalytical chemistry and vertebrate embryology using the frog Xenopus laevis as model, while elucidating the mechanism of action underlying cell fate changes by small molecules called metabolites. Our understanding of molecular mechanism orchestrating the patterning of the embryo requires knowledge of all the molecules produced as the zygote differentiates into the three primary germ layers of the embryo. Decades of research and innovative embryological manipulations have identified and revealed the functions of many genes and transcripts. However, very little is known about the contribution of metabolites to the formation of the intercellular communication and the long-term development of the embryo. The proposed training–research program fills this knowledge gap in technology and biology by providing the PhD Graduate Student with training to conduct original research at the chemistry-biology interface. The student will develop skills in bioanalytical chemistry, specifically quantitative metabolomics by capillary electrophoresis and ultrasensitive electrospray ionization mass spectrometry to enable the characterization of the proteo-metabolomic states of embryonic cells and tissues. Further, the student will also develop the required biomedical–biological skills to study the developmental implications of cell fate decisions, including classical embryological manipulations, cell fate tracking, and Xenopus laevis biology. The outcomes of this interdisciplinary approach will help illuminate the role of the metabolome for the establishment of these important precursor cells and tissues. Because these molecular processes are highly conserved across vertebrates, the data collected from Xenopus are likely to have high relevance to human structural birth defects. The new biochemical information that will be obtained in individual embryonic cells and their progeny (cell lineage) at several critical developmental time points will also improve other research fields that study cell differentiation (e.g., of stem cells) and the developmental origins of adult disease. This project will provide immersive cross-disciplinary training–research experience to enable the student to pursue an independent career while diversifying the biomedical research workforce.