Integrated Calendar

Cancer-associated fibroblasts (CAFs) are non-malignant tumor-supporting cells, which are highly abundant in the majority of carcinomas, and carry out distinct cancer related functions. The wide range of CAF activities suggests that CAFs are heterogenous and dynamically change. We analyzed CAFs using index and transcriptional single-cell sorting, at several time-points along breast tumor progression in mice, uncovering distinct subpopulations with transitioning transcriptional programs. We have further stained and analyzed sections of human breast tumors, and found that the two main CAF subpopulations are also present in human breast cancer, and that their ratio is associated with disease outcome

High-performance materials with elevated operating temperatures and robust mechanical properties, are essential for a wide variety of emerging applications, such as in functional adhesives, automobiles, aerospace, and coatings. Polyhexahydrotriazines (PHT) are new promising high-performance thermosets exhibiting enhanced thermal and mechanical properties.1 The performance and utility of PHT-based materials is further enhanced by the ability to design new material properties based on changes in the molecular structure.2 We demonstrated a new solvent-free approach for the fabrication of PHT based on low-melting-point diamines enabling the production of adhesives with comparable properties to well-established epoxy adhesives. Furthermore, these versatile materials could be degraded at different rates in acidic conditions based on the nature of the starting diamine molecular structure. Controlling the degradation is extremely valuable in composites and adhesives in order to be able to recycle and rework the materials.
In the second part of my talk I will show how the ability to control and adapt peptide conformation is crucial for the rational design and control of their function.3,4 We demonstrated by end-to-end distance measurements using Double Electron-Electron Resonance (DEER) EPR method that we can tune the conformations of the backbone while maintaining the sequence of the side-chains. Interestingly, tuning of the backbone has an effect on peptide propensity to aggregate or stabilize nanoparticles. Such knowledge is critical for designing new materials for various biotechnological applications.
1. J. M. García, G. O. Jones, K. Virwani, B. D. McCloskey, D. J. Boday, G. M. ter Huurne, H. W. Horn, D. J. Coady, A. M. Bintaleb, A. M. S. Alabdulrahman, F. Alsewailem, H. A. A. Almegren, J. L. Hedrick. Science 2014, 344, 732–735.
2. R. Kaminker, E. B. Callaway, N. D. Dolinski, S. M. Barbon, M. Shibata, H. Wang, J. Hu, C. J. Hawker. Solvent-Free Synthesis of High-Performance Polyhexahydrotriazine (PHT) Thermosets. Chem. Mater. 2018, 30, 8352–8358.
3. R. Kaminker, I. Kaminker, W. R. Gutekunst, Y. Luo, S.-H. Lee, J. Niu, C. J. Hawker, S. Han. Tuning Conformation and Properties of Peptidomimetic Backbones through Dual N/Cα-Substitution. Chem. Commun. 2018, 54, 5237–5240.
4. R. Kaminker, A. Anastasaki, W. R. Gutekunst, Y. Luo, S.-H. Lee, C. J. Hawker. Tuning of Protease Resistance in Oligopeptides through N-alkylation. Chem. Commun. 2018, 54, 9631–9634.

Sensory experience can change the structure and function of neurons in the brain over a wide range of timescales, from milliseconds-second modulation of synaptic activity to long-lasting alterations of genetic programs, lasting minutes to hours. While conversion of synaptic activity into long-lasting nuclear signaling is vital for learning and neuronal development, we still lack a clear understanding of its basic operating principles. To address this, I will describe recent advancements using two-photon fluorescence lifetime imaging and new biosensors which allowed us to image the activity of CREB, an activity-dependent transcription factor important for synaptic plasticity, at single cell resolution in awake mice. Simultaneous imaging of CREB and Ca2+ in the visual cortex permitted us to explore how sensory deprivation (dark-rearing) can modulate the sensitivity and duration of CREB activity to sensory-evoked Ca2+ elevations. Future work using this approach will allow us to unravel synapse to nucleus signaling dynamics underlying experience-dependent plasticity in the brain.

Soft matter systems offer a useful framework to study minimal models for living cells, helping to explain and quantify various aspects of biological functions in terms of macroscopic variables, symmetries, and universal properties. In this talk I will describe two such materials with particular focus on phenomena that arise when the system is near a phase transition. In the first part, I will describe a theoretical model of sound in lipid membranes near phase transition that corresponds to observations of nonlinear sound pulses in lipid monolayers as well as action potentials in living cells. Key properties are sigmoidal response to stimulation amplitude, and annihilation upon collision. I will explain the role of the phase diagram in producing the nonlinear properties and how sound in lipid membranes propagates thermal, electrical, and chemical variations in addition to the well-known mechanical changes. In the second part of the talk, I will describe a volume phase transition induced by the exchange of mono- and divalent cations in a polyelectrolyte hydrogel model. Ion-exchange and volume phase transition play a key role in several physiological functions where biopolymers are exposed to both mono- and multivalent counterions. These functions include, for instance, the packaging of DNA, andthe storage and release of cell secretory products. Our observations suggest that although the state diagram of the model system depends on many parameters of the gel and surrounding fluid, the volume phase transition exhibits universal properties. Osmotic swelling pressure measurements further reveal that both the second and third virial coefficients decrease with increasing divalent cation concentration until the volume transition is reached.

Artefacts that are found in archaeological excavations are often recognized by experts, who compare their appearance to other labeled objects that they have seen before or present in archaeological catalogs. Since this procedure may be subjective, scientific methods that aid archaeologists have become increasingly popular.
We have developed two machine learning tools which capture the similarity between two artefacts or similarities between groups of artefacts based on their RGB images. For the first antique recognition tool, we used face recognition deep neural network architecture, to measure the "archaeological" distance between images. In the second community detection tool, we aggregate similarities between images and measure the distance between assemblages - i.e., group of images. Based on that we applied a network-theory community detection algorithm, to find groups of archaeological sites that are linked to each other.
To test our methods, we used a highly diverse dataset of Israeli antiques. This dataset is a good case study due to geographical proximity between archaeological sites and the presence of artefacts from a wide range of archaeological ages.

Tissues are made up of cells and an extracellular matrix (ECM), a cross-linked network of fibers that exhibits complex mechanics. Cells actively alter the ECM structure and mechanics by applying contractile forces. These forces can propagate far into the matrix and allow for remote cellular sensing. We study experimentally and computationally how cell-generated forces are transmitted in fibrous environments, the associated physical mechanisms, and the ability of the propagated forces to support mechanical interaction between distant cells. Also, we demonstrate how the dynamic changes in the ECM structure can lead to improve transport of molecules traveling between the cells, facilitating mechano-biochemical interactions. Such long-range force interactions through the ECM can drive large-scale cooperative biological processes, such that occur during wound healing and morphogenesis. Our work can also provide design parameters for biomaterials used in tissue engineering applications.