In our lab, we are interested in identifying how cells in a multicellular organism interpret signals and make decisions, and how the decision-making process adheres to known engineering principles. The ultimate goal is to translate our knowledge to applications such as medicine, stem cell biology, and tissue engineering. Find out more…
Recent and Important News
Manuscript submitted on Maximally-Informed Design of Experiment
PhD student Razeen Shaikh is first author on a manuscript that was recently submitted. In this work, Razeen analyed a model of the TGF-β pathway, constrained by data for the Smad signaling protein Smad2 in human cells. She found that, even fitted to high quality experimental data, the model was underconstrained. Further analysis using experimental and simulated data showed that the next optimal experiment to perform would be to measure the co-Smad protein, Smad4. This work was an example of a general pipeline for optimal design of experiment. The manuscrsipt can be found online here at the preprint server, bioRχiv.
Paper published in Science Advances on the binding and clustering properties of Dorsal!
PhD student Sadia Siddika Dima is first author on a paper that was recently published in Science Advances. In this paper, Sadia used raster image correlation spectroscopy to quantify the absolute concentration of Dorsal in the nuclei of live, blastoderm-stage (1-3 hr old) Drosophila embryos. Crucially, this method also allowed her to distinguish between multiple subpopulations of Dorsal in the nuclei, including freely-diffusing Dorsal, DNA-bound Dorsal, and slowly-moving clusters of Dorsal. She also used single-particle tracking to trace the movement of these slowly-moving clusters. Interestingly, there appears to be a maximal concentration of freely-diffusing Dorsal, and above this concentration, Dorsal is allocated into either the DNA-bound or clustered pools. This concentration threshold may be a property of liquid-liquid phase separation. The paper was published in collaboration with Dr. Hernan Garcia at UC Berkeley and his former PhD student Dr. Meghan Turner, and can be found online here.
Paper published on the dynamics of transcription factors!
Graduate student Sadia Dima is first author on a recently-published paper in Development studying the dynamics of two crucial transcription factors in the early Drosophila embryo: Zelda and GAF. Sadia used a method called raster image correlation spectroscopy to measure the absolute concentration, binding, and mobility of these two transcription factors over a period of two hours in live embryos. With this work, she also was able to map out dose/response relationships for both of these transcription factors. The paper was published as a Research Report and can be found online here. Thanks to support from Texas A&M University, in agreement with the Company of Biologists, the paper was published as open access.
Paper on imaging of Cactus published!
The Reeves Lab has recently published a paper, together with the Williams lab at NCSU, analyzing the distribution of the Cactus/IκBα, which is an inhibitor of the Dorsal/NF-κB pathway in Drosophila. The paper, titled “Spatiotemporal dynamics of NF-κB/Dorsal inhibitor IκBα/Cactus in Drosophila blastoderm embryos,” is first-authored by Dr. Allison Schloop (a recent graduate of the Reeves lab with her Ph.D. in Genetics). In this paper, we use a novel imaging technique in which the protein of interest, Cactus, is fused with a small protein that dynamically binds GFP. In this way, the distribution of Cactus can be inferred from fluorescent images in live embryos. We also used the advanced imaging techniques “Fluorescence Recovery after Photobleaching” (FRAP) and “Raster Image Correlation Spectroscopy” (RICS) to measure the presence of Cactus in the nucleus. The paper can be found online at here at the open access Cell Press journal, iScience.
Paper on the mobility of Dorsal published as reviewed preprint in eLife
A team of researchers from the Reeves lab, in collaboration with the Sozzani lab at NCSU, has recently published a paper as a reviewed preprint in eLife in which we measure the mobility of Dorsal in early Drosophila embryos. The manuscript, co-first authored by former student Hadel Al Asafen, Dr. Sozzani’s former graduate student Natalie Clark, and former postdoc Etika Goyal, is titled “Dorsal/NF-κB exhibits a dorsal-to-ventral mobility gradient in the Drosophila embryo.” In this work, we use the advanced imaging technique known as “Raster Image Correlation Spectroscopy” (RICS) to measure the mobility and binding of Dorsal, and we find that Cactus is likely entering the nucleus to prevent Dorsal/DNA interactions. The manuscript can be found online at here.
Reeves lab receives NIH funding
The Reeves lab has recently received an R01 grant from the NIH (NIGMS) to study the dynamic interations between Dorsal and Cactus in the early fruit fly embryo. Dorsal is one of three fly homologs of NF-kappaB, which is a family of transcription factors that is responsible for developmental patterning, inflammation, and immunity across the animal kingdom. The inhibitor, Cactus, a homolog of IkappaB, binds to Dorsal and prevents it from entering the nucleus to regulate target genes. Studies have strongly suggested that cactus is itself a target gene of Dorsal, which would constitute a negative feedback loop. the Reeves lab will be studying the dynamics of this negative feedback loop. For more information, see here.
Paper submitted on feedback loops in stem cell differentiation
Graduate student Razeen Shaikh is first author on a recently-submitted manuscript studying a computational model of two feedback loops in the specification of stem cells in the Drosophila ovary. These two feeback loops regulate the BMP pathway in germline stem cells. The first feedback loop is negative feedback occuring in the stem cell itself. Razeen has found that this negative feedback ensures robustness of the decision for the stem cell to self-renew, and also increases the speed of response. The second loop is a positive feedback loop occuring in the daughter cell, known as the pre-cystoblast. This positive feedback loop acts in concert with the negative feedback loop to ensure that the pre-cystoblast differentiates, eventually forming the future egg. The manuscript can be found online at here at the preprint server, bioRχiv.
Paper published on the optimality of the BMP pathway
A collaborative team from the University of Notre Dame and Purdue, and led by the Reeves lab at Texas A&M, has recently published a paper analyzing the optimality of the Bone Morphogenetic Protein (BMP) pathway, which is responsible for multiple cellular outcomes, including differentiation and cell death. In the paper, with first author Razeen Shaikh and titled “Optimal Performance Objectives in the Highly Conserved Bone Morphogenetic Protein Signaling Pathway,” we analyze how a model of the pathway can achieve specific desired behaviors, such as a fast response time and noise filtering. We found these behaviors, called “Performance Objectives” (POs), compete with each other, so that it is crucial for cells to balance these POs in the best way possible for their situation. We suggest that cells can alter the balance of these POs by regulating the concentrations of key proteins in the pathway. The paper has been published in the journal npj: systems biology and applications and can be found online here.
Paper published on the dynamics of BMP signaling
A team of researchers from the Reeves lab, in collaboration with the Williams lab at NCSU, has recently published a paper analyzing the dynamics of the BMP pathway in early Drosophila embryos. The manuscript, co-first authored by former student Hadel Al Asafen and former postdoc Aydin Beseli, is titled “Dynamics of BMP signaling and stable gene expression in the early Drosophila embryo.” The is published in the Open Access journal Biology Open here. Update: see more in the press release here.
Reeves lab receives NSF funding
Dr. Reeves has led a team of researchers from Notre Dame and Purdue in securing funding from the NSF to study the Bone Morphogenetic Protein (BMP) signaling pathway across multiple species. The BMP pathway is highly conserved across the animal kingdom and is responsible for many different biological processes. In this project, we are asking the question of how the same signaling pathway can be responsible for multiple different kinds of outcomes. What is different between fruit fly embryos and human stem cells that the same pathway acts differently? A major goal of this work is to create a predictive mathematical model that is accurate to describe the behavior of the BMP pathway in three different species: fruit flies, zebrafish, and human cells. Read more here.
Dynamics of BMP signaling. Note the broad, weak signal early, that refines into a narrow, intense signal by the end.