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Upcoming Seminars

Giovanni D'Angelo, PhD - "Single-Cell in situ Lipidomics reveals a role for Cell-to-Cell Lipid Heterogeneity in the maintenance of cell identity"

Kristian Gerhard Jebsen Chair on Metabolism, Institute of Bioengineering, Laboratory of Lipid Cell Biology, EPFL-SV-IBI, Swiss Federal Institute of Technology Lausanne (EPFL), Lausanne, Switzerland
When Jan 29, 2020
from 12:00 PM to 01:30 PM
Where Tigem, Auditorium Vesuvius
Contact Name
Contact Phone 08119230659
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Abstract
Eukaryotic cells produce thousands of lipids each potentially contributing to specific biological functions. With the development of lipidomics we now appreciate the lipid compositional complexity of the cell, and start making sense of lipidome dynamics. Lipidomes indeed vary among cell types and are reprogrammed in differentiation events. Moreover, lipid composition is subjected to cell-to-cell variation in syngeneic and otherwise homogeneous cell populations suggesting that lipid heterogeneity contributes to the emergence of multicellular patterns. Lipid biologists have so far addressed lipidomes in bulk cell extracts or selected lipids at the single-cell level. Thus, how lipidomes vary form one cell to another and which cell-to-cell lipid variations have biological meaning remains to be defined. Here by using high-resolution mass spectrometry imaging we have imaged a sizable fraction of the lipidome of hundreds of individual cells in culture. By this approach we found that: (i) specific lipid metabolic segments are subjected to high cell-to-cell variability; (ii) cell-to-cell lipid variability marks discrete cellular states; (iii) and that highly variable lipids participate to cell fate/ cell state determination. Altogether our data reveal a role for specific single-cell lipid metabolic trajectories in determination and maintenance of cell identity in multicellular contexts.

 

Gaetano Gargiulo, PhD - "Tumor homeostates revealed by synthetic locus control regions"

Molecular Oncology, Max-Delbrück-Center for Molecular Medicine (MDC), Berlin, Germany
When Feb 03, 2020
from 12:00 PM to 01:30 PM
Where Tigem, Auditorium Vesuvius
Contact Name
Contact Phone 08119230659
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Abstract
Our understanding of developmental and disease homeostasis requires genetic tracing to selectively identify cellular states and fate transitions without perturbing them. I will discuss a method we invented and developed to translate multifactorial signatures representing cellular states into synthetic genetic tracing cassettes. Using synthetic locus control regions (sLCRs), we investigated the cellular and  molecular basis underlying glioblastoma heterogeneity by genetically tracing tumor cells adopting similar states under homeostatic conditions in vitro and in vivo. Cell fate tracing by sLCRs demonstrates that the proneural glioblastoma is a hardwired identity. Instead, the mesenchymal glioblastoma is a metastable state downstream pro-inflammatory and differentiation cues, genetically- and pharmacologically-tunable and similarly wired in breast and lung tumors. Notably, we discovered that innate immune cells divert glioma cells into a specific mesenchymal  state causal to therapeutic resistance. I will show evidence that the same approach is potentially valid also to report on the cellular response to stress. Hence, this simple, automated and scalable strategy advances genetic tracing of intrinsic cell states, adaptive responses and pharmacogenomics in development and disease.

Giuseppe Matarese, MD, PhD - "Metabolic basis for immunological self-tolerance and susceptibility to infections"

Professor of Immunology, Treg Cell Lab, Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli "Federico II" and IEOS-CNR, Napoli - Italy
When Feb 11, 2020
from 12:00 PM to 01:15 PM
Where Tigem, Auditorium Vesuvius
Contact Name
Contact Phone 08119230659
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Abstract
The field that links immunity and metabolism is rapidly expanding. Non-immunological disorders such as obesity and type 2 diabetes have been linked to immune dysregulation suggesting that metabolic alterations can be induced by or be consequence of an altered immunological self-tolerance. In this context, a key role is played by signaling systems acting as “metabolic sensors” linking energy/nutritional status with innate and adaptive immune cell functions. In this context, the adipose-tissue derived hormone leptin plays a major role.

T cell sensing of metabolic and energetic changes in the microenvironment can affect their differentiation, maturation, and activation. We have recently shown that metabolic manipulation of CD4+CD25- conventional T (Tconv) cells either via inhibition of mTOR or via leptin blockade, causes a defined transcriptional signature that determines the outcome of the response, including proliferation and effector functions. Further, we have analyzed the transcriptional response of CD4+CD25+Foxp3+  regulatory T (Treg) cells to the leptin-mTOR inhibition that was found dramatically different compared to Tconv cells, because it caused up-regulation of cell-proliferation signaling. These results strengthen the link between nutritional status and T cell activity, identifying the leptin–mTOR axis as a potential target for modulating Tconv/Treg balance in normal and pathologic conditions such as infections, autoimmunity and metabolic disorders (ie. obesity). Also, the involved gene signatures affected not only pathways of adaptive immunity but also those of innate immune responses thus suggesting an involvement of metabolism on immunity as “a whole”. The possibility to interfere, via metabolic manipulation and immunometabolism, on innate and adaptive immune responses should lead to novel approaches to treat different pathologic conditions such as infections, inflammation and autoimmunity.