Events

Nine out of every ten cancer-related deaths is caused by metastasis, but the molecular mechanisms driving this process are still not fully understood. Several studies have implicated that as a cell’s metastatic potential increases, cell stiffness decreases. Yet while certain genes that affect cell mechanics have been studied, a genome-wide study of networks that modulate […]

Perhaps the defining feature of the eukaryotic cell is its organization into membrane-bound compartments known as organelles. While the processes underlying the biogenesis of individual organelles are often well-known the precision with which individual cells exert quantitative control over individual organelle properties, such as number and size, and coordinate these properties at systems-scale across the […]

Single-cell genomics technologies have been lauded for their potential to probe biological systems with cell type specificity, and to elucidate cellular differentiation trajectories. However, the analysis of single-cell genomics data is fraught with numerous computational challenges. I will show that biophysical models of transcriptional dynamics are helpful in resolving some of these challenges and outline […]

BRAF-mutant melanoma cells under prolonged BRAF inhibition have been shown to enter a state of balanced division and death, termed "idling."It is hypothesized that the idling state acts as a haven into which cancer cells can escape to survive drug treatments and that idling cells eventually acquire genetic resistance mutations, driving tumor recurrence. There may […]

Even isogenic bacteria may heterogeneously express different subsets of genes, assuming distinct roles for the survival of the community. There is limited knowledge about the diversity of phenotypic states within complex bacterial communities which are ill-suited for reporter-based approaches. Overcoming technical challenges associated with bringing the technology used for eukaryotic cells to prokaryotes, we developed […]

Modern fluorescence labeling and optical microscopy approaches make it possible to observe every stage of basic gene regulatory processes, even at the level of individual DNA, RNA, and protein molecules, in living cells, and within fluctuating environments. To complement these observations, the mechanisms and parameters of discrete stochastic models can be rigorously inferred to reproduce […]

The most prevalent, devastating, and complex diseases of our time, such as diabetes, cardiovascular disease, cancer, and infectious diseases, involve the dynamic interactions of cells with one another and with their changing environment. However, the drugs we typically use to treat diseases target a single protein and disregard the fact that cells within tissues are […]

Signaling mechanisms enable cells to sense, respond, and adapt to changing environments. Understanding signal transduction mechanisms at both molecular and network levels is critical to characterize key proteins and reaction rates in the cellular response in normal and pathophysiological conditions. This insight is important to discover unknown regulatory mechanisms, to identify abnormal protein interactions, and […]

Many pathways involved in innate immunity in plants, insects, and mammals also play roles in host development. This genetic pleiotropy could constrain the ability of immune systems to rapidly evolve in response to selective pressure from microbes because adaptive evolution could negatively affect other developmental processes and thus host fitness. Does pleiotropy constrain adaptive evolution, […]

Biotechnology is rapidly improving, largely due to our ability to manipulate genetic material and efficiently measure biological processes. This talk will describe advances in computational approaches and experimental platforms to probe and control stochastic biological processes within individual cells under a microscope. First, I will describe a novel platform for interfacing individual cells with computational models of […]

Microscopic imaging techniques have given us access to high fidelity measurements of subcellular molecule and protein mass distributions. Quantitative analysis of these has the potential to elucidate biological mechanisms as well help perform diagnosis and clinical outcome predictions in cancer and other pathologies. By using the mathematics of optimal transport we can quantitatively compare distributions […]

Somatic evolution is increasingly being recognized as the main driver not only in cancer progression but importantly in the emergence of resistance to existing treatments. Much of the focus in the research of evolution in cancer has been devoted to leveraging existing -omics tools to evaluate how tumors change but Darwinian evolution requires us to […]

Agent-based models simulate individual cells as software objects, each with their own independent states and behavioral “rules” that codify our biological hypotheses. Generally, they also are tied to models of the chemical microenvironment to emulate the motion of oxygen, growth and signaling factors, and therapeutic compounds. Together, these can form a “virtual laboratory” to computational […]

Long noncoding RNAs (LncRNAs) are increasingly recognized as being involved in human physiology and diseases, but there is a lack of mechanistic understanding for the majority of lncRNAs. We comparatively tested proposed mechanisms of antisense lncRNA regulation at the X-chromosome Inactivation (XCI) locus. Our single-cell analyses argue against mechanisms that require the Xist or Tsix […]