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Page 1 of 2 12 >>

September 01 - September 30

12 entries found

Talk by Pro..
Start date: September 05
04:00 pm 05:00 pm

Local Nucle..
Start date: September 12
11:00 am 12:00 pm

Epigenetic ..
Start date: September 12
04:00 pm 05:00 pm

Description: 

Abstract

DNA methylation based biomarkers of aging known as collectively as "epigenetic clock" can be used to measure the age of any human tissue, cell type, or fluid that contains DNA. DNA methylation age captures aspects of biological age, e.g. it predicts lifespan and healthspan in large scale epidemiological studies. I will describe several new epigenetic clocks for humans and other mammals. The skin & blood clock (based on 391 CpGs) is tailor-made for human fibroblasts, keratinocytes, buccal cells, endothelial cells, lymphoblastoid cells, skin, blood, and saliva samples. Gestational age correlates with DNAm age in cord blood. When used on fibroblasts from Hutchinson Gilford Progeria Syndrome patients, this age estimator (referred to as the skin & blood clock) uncovered an epigenetic age acceleration with a magnitude that is below the sensitivity levels of other DNAm-based biomarkers.

Arguably the strongest predictor of lifespan, DNAm GrimAge, is a composite biomarker based on seven DNAm surrogates of plasma protein levels and a DNAm-based estimator of smoking pack-years. Using large-scale validation data from thousands of individuals, we demonstrated that DNAm GrimAge stands out among existing epigenetic clocks in terms of its predictive ability for time-to-death ( P=2.0E-75), time-to-coronary heart disease (P=6.2E-24), time-to-cancer (P=1.3E-12), its strong relationship with computed tomography for fatty liver/excess visceral fat, and age-at-menopause (P=1.6E-12).Recent genomewide association studies of epigenetic age acceleration shed light on the genetic underpinnings of the epigenetic clock (e.g. Lu et al 2016, PMID: 26830004). The epigenetic clock method has been used in several applications including obesity, Down syndrome, cognitive decline, HIV, Parkinson's disease, and centenarians.

5 most important publications

1. Horvath S (2013) DNA methylation age of human tissues and cell types. Genome Biol. 2013 Oct 21;14(10):R115. PMCID: PMC4015143

2. Horvath S, Raj K DNA methylation-based biomarkers and the epigenetic clock theory of ageing. Nat Rev Genet. 2018 Jun;19(6):371-384. doi: 10.1038/s41576-018-0004-3. PMID: 29643443

3. Lu AT et al (2019) DNA methylation GrimAge strongly predicts lifespan and healthspan. Aging (Albany NY). 2019 Jan 21. doi: 10.18632/aging.101684. PMID: 30669119 https://www.aging-us.com/full/101684

4. Lu et al 2018. GWAS of epigenetic aging rates in blood reveals a critical role for TERT. Nat Commun. 2018 Jan 26;9(1):387. doi: 10.1038/s41467-017-02697-5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5786029/

5. Horvath et al 2018. Epigenetic clock for skin and blood cells applied to Hutchinson Gilford Progeria Syndrome and ex vivo studies. Aging (Albany NY). 2018 Jul 26;10(7):1758-1775. doi: 10.18632/aging.101508 https://www.aging-us.com/full/10/1758

Everybody is very welcome!

Transnetys ..
Start date: September 17
02:00 pm 03:00 pm

Description: 

Please register via: Transnetyx.com/presentation/44

Interaction..
Start date: September 17
03:00 pm 04:00 pm

Fluoreszenz..
Start date: September 18
10:00 am 11:30 am

Printed 3D ..
Start date: September 19
04:00 pm 05:00 pm

Incorporati..
Start date: September 20
04:00 pm 06:00 pm

Description: 

Many blinding diseases result in the loss of non-regenerable photoreceptors. A promising strategy to restore vision is to replace lost cells with stem cell-derived photoreceptors. Human vision is particularly reliant on cone-mediated high-acuity and colour vision. Here, we enriched and transplanted a purified cone population through the use of a highly specific human iPSC cone reporter line. The incorporation and maturation of cells into the host retina was assessed through immunohistochemistry, electron microscopy and next generation sequencing providing evidence for longterm survival and maturation of in vitro human cones in mouse models of retinal degeneration.

Followed by Social Hour!

EMT-induced..
Start date: September 20
04:00 pm 06:00 pm

Description: 

To undergo mitosis successfully, animal cells need to acquire a round shape to provide space for the mitotic spindle. This mitotic rounding relies on mechanical deformation of surrounding tissue and is driven by forces emanating from actomyosin contractility. Cancer cells are able to maintain successful mitosis in mechanically challenging environments such as the increasingly crowded environment of a growing tumor, thus, suggesting an enhanced ability of mitotic rounding in cancer. Here, we show that epithelial mesenchymal transition (EMT), a hallmark of cancer progression and metastasis, gives rise to a cell-cycle dependent cell-mechanical switch and enhanced mitotic rounding strength in breast epithelial cells. Furthermore, we show that this cell-mechanical change correlates with a strong EMT-induced change in the activity of Rho GTPases RhoA and Rac1. Accordingly, we identify Rac1 as a cell-cycle dependent regulator of actin cortex mechanics. Our findings hint at a new role of EMT in successful mitotic rounding and division in mechanically confined environments such as a growing tumor.

Followed by Social Hour!

A molecular..
Start date: September 26
04:00 pm 05:00 pm

Description: 

Abstract
Despite the importance of microtubules in cell division and cell migration, and the fact that they are targets of a number of anticancer drugs, the molecular mechanism of microtubule dynamic instability is not understood. Using Interferometric Scattering Microscopy to visualize gold nanoparticle-labeled tubulin incorporating into growing microtubules, we are able to directly measure the on- and off-rates for tubulin incorporation into the microtubule lattice, and thus provide new quantitative constraints for models of dynamic instability.  We are also investigating the regulation of dynamic instability by mitotic kinesins from the kinesin-5 family.  We find that kinesin-5 enhances microtubule polymerization by stabilizing a straight conformation of tubulin.  These high-resolution studies will be discussed in the context of the numerous roles of microtubules in cells.


5 most important publications
Direct observation of individual tubulin dimers binding to growing microtubules. Mickolajczyk, K. J., E. A. Geyer, T. Kim, L. M. Rice, and W. O. Hancock. 2019. Proc Natl Acad Sci U S A 116:7314-7322.

Kinesin-5 Promotes Microtubule Nucleation and Assembly by Stabilizing a Lattice-Competent Conformation of Tubulin.Chen, G. Y., J. M. Cleary, A. B. Asenjo, Y. Chen, J. A. Mascaro, D. F. J. Arginteanu, H. Sosa, and W. O. Hancock. 2019. Curr Biol 29:2259-2269 e2254.

Kinetics of nucleotide-dependent structural transitions in the kinesin-1 hydrolysis cycle. 2015. Mickolajczyk, K. J., N. C. Deffenbaugh, J. Ortega Arroyo, J. Andrecka, P. Kukura, and W. O. Hancock. Proc. Natl. Acad. Sci., 112:E7186-7193.  PMID: 26676576

Kinesin-5 is a microtubule polymerase. 2015. Chen, Y., and W.O. Hancock. Nature Communications 6:8160. doi:10.1038/ncomms9160.  PMID: 26437877

Bidirectional cargo transport: moving beyond tug of war. Hancock W.O. 2014. Nat Rev Mol Cell Biol. 15(9):615-28.  PMID: 25118718

Everybody is very welcome!

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