Elucidating the Cam broadcast free
requirement have the highest proliferative potency. Self-renewal via asymmetrical cell division (ACD) is vital for maintenance of HSC numbers and perturbation of this process can lead to an impaired hematopoietic system, with subsequent blood diseases such as acute leukemia and/or bone marrow failure.How and which HSCs are programmed for ACD remain central and unanswered questions.Voltage controlled magnetic anisotropy (VCMA) is an efficient way to manipulate the magnetization states in nanomagnets, promising for low-power spintronic applications.The underlying physical mechanism for VCMA is known to involve a change in the d-orbital occupation on the transition metal interface atoms with an applied electric field.However, a simple qualitative picture of how this occupation controls the magnetocrystalline anisotropy (MCA) and even why in certain cases the MCA has opposite sign still remains elusive.In this paper, we exploit a simple model of orbital populations to elucidate a number of features typical for the interface MCA and the effect of electric field on it, for 3d transition metal thin films used in magnetic tunnel junctions.In this regime we predict a significantly enhanced VCMA which exceeds 1p J/Vm.
The underlying genetic architecture of the disorder is broad and exome sequencing of familial ALS samples (found in approximately 10% of total cases) has successfully identified six new ALS genes over the last five years eg. Our group has recently identified another novel ALS gene, ANXA11 (recently published in Sci Transl Med. Annexin A11 (encoded by ANXA11) is a phospholipid and calcium binding protein, in which ALS mutations form insoluble aggregates in-vitro and in post-mortem tissue that also abolish binding to calcyclin.
We have demonstrated that the endocytic protein, Ap2a2 distinguishes an asymmetrical from a symmetrical cell division during HSC mitoses, and when overexpressed enhances mouse HSC activity.
Ap2a2 is a component of the Adaptor protein 2 complex that functions in clathrin-dependent endocytosis of receptors and nutrient cargo.
The tetracycline-induceable H2B-GFP mouse (Foudi A. et al, Nature Biotech 2009) has revealed functional heterogeneity within the CD150 LT-HSCs but that Ap2a2 overexpression increases the fraction of this specific subpopulation from 20% to 60% at plus 20 weeks post-transplantation.
To identify novel genes and pathways driving LT-HSC function and self-renewal, we are currently performing comparative gene expression analyses from the subpopulation of Ap2a2-transduced against control, vector-transduced GFPCD150 48-LSK LT-HSCs.
The student will investigate the interaction of Annexin A11 and Calcyclin and conduct structural analysis using Biophysical Structural Binding Experiments with WT and Annexin A11 mutants e.g. Further investigation will be conducted in-vitro using cell lines, primary mouse cell lines, i PSCs and will characterize sub-cellular localization of Annexin A11/mutants and calcyclin, conduct apoptosis and calcium assays, and address the relationship of Annexin A11 with TDP43 pathology.