Binary Cellular Biology of Human Growth

Authors:

Aidan Wang, James Michaelson

Date Created:

2025-01-01

Course Title:

Professor:

Not specified

About Paper:

Understanding how singular cell zygote transforms into a multi- developing a new method called Binary Cellular Fetal Growth cellular organism has been a central question in biology for Analysis to better understand the relationship between the rate centuries. It is known that a growing embryo’s cells divide at of growth of fetuses and the size of the baby post-birth. This an exponential fashion but become mitotically restrained as an can be done through examining the birthweight parameter of adult. This change in cellular division, including survival and the binary cellular universal growth equation and how it may death rates in units of number of cells, can be better understood reflect endocrinological control of growth. By comparing cellular using a novel approach called Binary Cellular Analysis, which values of different animals and humans, these findings reveal captures this phenomenon using the binary cellular mitotic fractionpossibilities for the detection and pharmacological treatment of equation. This approach can be furthered by specifically applying fetuses that grow too fast or too slowly, as well as new ways to this method to learn more about human fetuses and can provide help obstetricians guide each fetus to a birthweight and fetal age essential information for the management of the health of the that has the lowest possible chance of complication. newborn and its mother. This summer, we are working on Genetically Engineering Riboswitch-Regulated RNA Systems for Space Applications: Optimizing Microbial Survival and Resource Preservation in Simulated Extraterrestrial Environments Justen Wen, Xavier Portillo, Robin Wordsworth, George Church Harvard College | Leverett House | Biomedical Engineering | 2028 Space exploration presents extreme environmental challenges, allowingreal-timemetabolicadjustmentsinresponsetofluctuating including pressure differentials, radiation exposure, and limited levelsofions, smallmolecules, metabolites, andUVlight. Wewill resource availability. To address these challenges, we aim to implement Multiplex Automated Genome Engineering (MAGE) genetically engineer organisms to enhance oxygen production, and plasmid driven in vivo directed evolution to construct and biofuel synthesis, and bioplastic generation for sustainable genetically modify the organisms. Our aim is to select metabolic space missions. RNA and mRNA genetic engineering enables pathways for modular metabolisms for translational efficiency precise, efficient, and tunable regulation of gene expression which will increase resource efficiency. Experimental variation with modular expression from riboswitches allowing for diverse includes simulated space conditions such as variable pressure, biological applications. We will use directed evolution and high-radiation, and variable CO 2evels, exploring how UTR and design 5′-untranslated regions (UTRs) and riboswitches to riboswitch modifications can create sustainable engineered strains select for dynamically regulated gene expression in response to with optimized resource capacities. This approach will contribute environmental stressors. Using UTR evolution and design, we to self-sustaining biomanufacturing in space, paving the way for aim to improve translation efficiency, stress adaptation through long-term space colonization and sustainable bioprocessing on riboswitch modular gene regulation, with the goal of ensuring Earth, while also exploring the origins of life through improving microbial survival and productivity in extraterrestrial conditions.the understanding of RNA structural evolution. Additionally, synthetic riboswitches will act as molecular sensors, Spatio-temporal and Functional Analysis of EGF Signalling in Initiation of Intestinal Adenomas. Olivia Wright, Krithika Badarinath, Ramesh Shivdasani Emmanuel College, University of Cambridge | Molecular and Cellular Biology | 2026 WNT pathway hyperactivation, usually by mutation of the Apc mouse intestinal organoids. From 7 to 21 days after induction gene, in intestinal stem cells (ISCs) causes adenomas, the benign of Apc mutation (dpi) in ISCs, Epiregulin and Neuregulin-1 obligate precursors of colorectal cancer. To form adenomas, were upregulated in the mesenchyme surrounding developing multiple neighboring mutant intestinal crypts must first cooperate adenomas; Amphiregulin was most increased in epithelial cells with each other, likely through intervening mesenchymal cells. in the same time frame. In contrast, Apc ;Ascl2 -/-intestines The signals that constitute this dialog among crypts are currently showed increased ligand expression until 7 dpi, followed by a unknown. Crypts lacking the transcription factor ASCL2 fail sharpdecline. ThesefindingsindicatethatASCL2initiallyrestrains to form adenomas and can therefore help identify those signals. and subsequently sustains local EGF signaling during initial stages Mouse mesenchymal cells near Apc crypts increase expression of of adenoma formation. Addition of Epiregulin or Neuregulin- epidermal growth factor (EGF) ligands Epiregulin, Amphiregulin, 1 rescued Apc ;Ascl2 -/-organoid deficiencies (Tukey’s HSD, and Neuregulin-1, which are strong candidate mediators of crypt- p = 0:0149), revealing their permissive role in epithelial crypt communication. Expression of these ligands currently cell proliferation. Thus, Apc-mutant ISCs use the transcription lacks spatiotemporal resolution and their functions in adenoma factor ASCL2 to elevate local expression of EGF ligands, hence development are unproven. We used in situ hybridization promoting tumorigenic communication between nearby mutant to localise these ligand mRNAs across time in Apc -/-and crypts and driving adenoma formation. Pharmacologic disruption -/- -/- Apc ;Ascl2 intestines and tested each ligand’s abili-/-to re-/-eof this cell-cell signaling is therefore a potential strategy to arrest organoid growth, a proxy for adenoma formation, in Apc ;Ascl2 early adenoma formation by Apc-mutant intestinal crypts.

Abstract:

Understanding how singular cell zygote transforms into a multi- developing a new method called Binary Cellular Fetal Growth cellular organism has been a central question in biology for Analysis to better understand the relationship between the rate centuries. It is known that a growing embryo’s cells divide at of growth of fetuses and the size of the baby post-birth. This an exponential fashion but become mitotically restrained as an can be done through examining the birthweight parameter of adult. This change in cellular division, including survival and the binary cellular universal growth equation and how it may death rates in units of number of cells, can be better understood reflect endocrinological control of growth. By comparing cellular using a novel approach called Binary Cellular Analysis, which values of different animals and humans, these findings reveal captures this phenomenon using the binary cellular mitotic fractionpossibilities for the detection and pharmacological treatment of equation. This approach can be furthered by specifically applying fetuses that grow too fast or too slowly, as well as new ways to this method to learn more about human fetuses and can provide help obstetricians guide each fetus to a birthweight and fetal age essential information for the management of the health of the that has the lowest possible chance of complication. newborn and its mother. This summer, we are working on Genetically Engineering Riboswitch-Regulated RNA Systems for Space Applications: Optimizing Microbial Survival and Resource Preservation in Simulated Extraterrestrial Environments Justen Wen, Xavier Portillo, Robin Wordsworth, George Church Harvard College | Leverett House | Biomedical Engineering | 2028 Space exploration presents extreme environmental challenges, allowingreal-timemetabolicadjustmentsinresponsetofluctuating including pressure differentials, radiation exposure, and limited levelsofions, smallmolecules, metabolites, andUVlight. Wewill resource availability. To address these challenges, we aim to implement Multiplex Automated Genome Engineering (MAGE) genetically engineer organisms to enhance oxygen production, and plasmid driven in vivo directed evolution to construct and biofuel synthesis, and bioplastic generation for sustainable genetically modify the organisms. Our aim is to select metabolic space missions. RNA and mRNA genetic engineering enables pathways for modular metabolisms for translational efficiency precise, efficient, and tunable regulation of gene expression which will increase resource efficiency. Experimental variation with modular expression from riboswitches allowing for diverse includes simulated space conditions such as variable pressure, biological applications. We will use directed evolution and high-radiation, and variable CO 2evels, exploring how UTR and design 5′-untranslated regions (UTRs) and riboswitches to riboswitch modifications can create sustainable engineered strains select for dynamically regulated gene expression in response to with optimized resource capacities. This approach will contribute environmental stressors. Using UTR evolution and design, we to self-sustaining biomanufacturing in space, paving the way for aim to improve translation efficiency, stress adaptation through long-term space colonization and sustainable bioprocessing on riboswitch modular gene regulation, with the goal of ensuring Earth, while also exploring the origins of life through improving microbial survival and productivity in extraterrestrial conditions.the understanding of RNA structural evolution. Additionally, synthetic riboswitches will act as molecular sensors, Spatio-temporal and Functional Analysis of EGF Signalling in Initiation of Intestinal Adenomas. Olivia Wright, Krithika Badarinath, Ramesh Shivdasani Emmanuel College, University of Cambridge | Molecular and Cellular Biology | 2026 WNT pathway hyperactivation, usually by mutation of the Apc mouse intestinal organoids. From 7 to 21 days after induction gene, in intestinal stem cells (ISCs) causes adenomas, the benign of Apc mutation (dpi) in ISCs, Epiregulin and Neuregulin-1 obligate precursors of colorectal cancer. To form adenomas, were upregulated in the mesenchyme surrounding developing multiple neighboring mutant intestinal crypts must first cooperate adenomas; Amphiregulin was most increased in epithelial cells with each other, likely through intervening mesenchymal cells. in the same time frame. In contrast, Apc ;Ascl2 -/-intestines The signals that constitute this dialog among crypts are currently showed increased ligand expression until 7 dpi, followed by a unknown. Crypts lacking the transcription factor ASCL2 fail sharpdecline. ThesefindingsindicatethatASCL2initiallyrestrains to form adenomas and can therefore help identify those signals. and subsequently sustains local EGF signaling during initial stages Mouse mesenchymal cells near Apc crypts increase expression of of adenoma formation. Addition of Epiregulin or Neuregulin- epidermal growth factor (EGF) ligands Epiregulin, Amphiregulin, 1 rescued Apc ;Ascl2 -/-organoid deficiencies (Tukey’s HSD, and Neuregulin-1, which are strong candidate mediators of crypt- p = 0:0149), revealing their permissive role in epithelial crypt communication. Expression of these ligands currently cell proliferation. Thus, Apc-mutant ISCs use the transcription lacks spatiotemporal resolution and their functions in adenoma factor ASCL2 to elevate local expression of EGF ligands, hence development are unproven. We used in situ hybridization promoting tumorigenic communication between nearby mutant to localise these ligand mRNAs across time in Apc -/-and crypts and driving adenoma formation. Pharmacologic disruption -/- -/- Apc ;Ascl2 intestines and tested each ligand’s abili-/-to re-/-eof this cell-cell signaling is therefore a potential strategy to arrest organoid growth, a proxy for adenoma formation, in Apc ;Ascl2 early adenoma formation by Apc-mutant intestinal crypts.

Source:

Harvard / Jessie Wang, Lauren Cooke, Vineet Raghu / 2025

Topics:

cellular, adenoma, apc, cell, crypt, growth, expression, space, ascl2, ligand, binary, intestinal

Co-authors:

@aidanwang379 , @jamesmichaelson380