Walter and Eliza Hall Institute of Medical Research

About: Walter and Eliza Hall Institute of Medical Research is a nonprofit organization based out in Melbourne, Victoria, Australia. It is known for research contribution in the topics: Antigen & Immune system. The organization has 5012 authors who have published 10620 publications receiving 873561 citations.

Ionizing radiation and the immune response.

Abstract: Publisher Summary This chapter illustrates several ways in which radiation may be employed to dissect several individual cellular components of the immune response. The chapter considers the interrelationships between radiation and the various components of the immune response from three perspectives: (1) the effect of irradiation on normal lymphoid tissues and on isolated lymphocytes, (2) the effect of irradiation on antibody production, transplantation immunity, and other forms of cellular immunity, and (3) the effect of irradiation upon tolerance with specific references to putative autoimmune consequences after radiation-induced alterations in normal immunological homeostasis. A wide variety of approaches are available to characterize and define distinct populations of lymphocytes. These include biophysical and functional methods and characterization of antigenic and cell surface receptor components. The mechanisms of radiation effects in biological systems, particularly in humans, have been derived from experiments utilizing cells exposed in vitro and maintained in tissue culture. Such cells can be examined for: (1) loss of viability, (2) alterations in biophysical structure, (3) loss of functional capabilities, (4) biochemical changes, and (5) evidence of injury to subcellular components.

An integrated expression atlas of miRNAs and their promoters in human and mouse.

Abstract: MicroRNAs (miRNAs) are short non-coding RNAs with key roles in cellular regulation. As part of the fifth edition of the Functional Annotation of Mammalian Genome (FANTOM5) project, we created an integrated expression atlas of miRNAs and their promoters by deep-sequencing 492 short RNA (sRNA) libraries, with matching Cap Analysis Gene Expression (CAGE) data, from 396 human and 47 mouse RNA samples. Promoters were identified for 1,357 human and 804 mouse miRNAs and showed strong sequence conservation between species. We also found that primary and mature miRNA expression levels were correlated, allowing us to use the primary miRNA measurements as a proxy for mature miRNA levels in a total of 1,829 human and 1,029 mouse CAGE libraries. We thus provide a broad atlas of miRNA expression and promoters in primary mammalian cells, establishing a foundation for detailed analysis of miRNA expression patterns and transcriptional control regions.

Strikingly Different Clinicopathological Phenotypes Determined by Progranulin-Mutation Dosage

Abstract: We performed hypothesis-free linkage analysis and exome sequencing in a family with two siblings who had neuronal ceroid lipofuscinosis (NCL). Two linkage peaks with maximum LOD scores of 3.07 and 2.97 were found on chromosomes 7 and 17, respectively. Unexpectedly, we found these siblings to be homozygous for a c.813_816del (p.Thr272Serfs∗10) mutation in the progranulin gene (GRN, granulin precursor) in the latter peak. Heterozygous mutations in GRN are a major cause of frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP), the second most common early-onset dementia. Reexamination of progranulin-deficient mice revealed rectilinear profiles typical of NCL. The age-at-onset and neuropathology of FTLD-TDP and NCL are markedly different. Our findings reveal an unanticipated link between a rare and a common neurological disorder and illustrate pleiotropic effects of a mutation in the heterozygous or homozygous states.

NKX2-5 eGFP/w hESCs for isolation of human cardiac progenitors and cardiomyocytes

Abstract: NKX2-5 is expressed in the heart throughout life. We targeted eGFP sequences to the NKX2-5 locus of human embryonic stem cells (hESCs); NKX2-5(eGFP/w) hESCs facilitate quantification of cardiac differentiation, purification of hESC-derived committed cardiac progenitor cells (hESC-CPCs) and cardiomyocytes (hESC-CMs) and the standardization of differentiation protocols. We used NKX2-5 eGFP(+) cells to identify VCAM1 and SIRPA as cell-surface markers expressed in cardiac lineages.