Seminars | This Week

IMB Seminar Series

Date/Time: Friday 29th June 2018 12:30

Location: QBP Auditorium, Bld 80

Title of talk: Bone and marrow resident macrophages regulate both hematopoietic and skeletal health and regeneration
Speaker's name: A/Prof Allison Pettit
Speaker's organisation: Mater Research Institute-UQ
Talk abstract: Bone and bone marrow (BM) are interdependent organs with reciprocal regulatory functions throughout life. Bone and BM contain multiple functionally distinct resident macrophage subsets, including haematopoietic stem cell (HSC) niche macrophages and osteal tissue macrophages (osteomacs). Using multiple in vivo and ex vivo strategies we have demonstrated that osteomacs and HSC niche macrophages play an integral roles in regeneration of bone and bone marrow after injury. Consequently macropahges represent an attractive cellular target to promote bone and bone marrow repair after acute injury or as a consequence of age-mediated functional decline.

Host name: Professor Matt Sweet
Host email: imbevents@uq.edu.au

Seminars | This Week

IMB Friday Noon Seminar

Date/Time: Friday 6th July 2018 12:00

Location: QBP Auditorium

Title of talk: A view into human kidney morphogenesis using stem cells
Speaker's name: Prof. Melissa Little
Speaker's organisation: Murdoch Children's Research Institute
Talk abstract: The capacity to generate a pluripotent stem cell from any somatic cell type has revolutionalised stem cell biology. The development of protocols for the stepwise differentiation of such pluripotent cells, not only to specific cellular endpoints but complex 3D organoids representative of developing human tissues, completely changes the future prospects of stem cell medicine. It is hoped that such stem cell-derived human tissue will drive personalised disease modelling, toxicity and screening, cell therapy and even tissue bioengineering. It is also hoped that this will provide a window into human development not previously available and potentially allow the dissection of the biophysical requirements for tissue self-organisation. All this will depend upon how reliably these models mirror normal human development at the level of cellular identity, multicellular complexity and functional maturation. We have developed a protocol for the generation of kidney organoids (Takasato et al, Nature, 2015) from human pluripotent stem cells. This protocol relies upon the stepwise recapitulation of morphogenetic events previously characterised during normal kidney development in the mouse. Hence, the validity of the model remains to be investigated. Using CRISPR-Cas9 editing, we have developed a suite of reporter lines that is now allowing us to query the accuracy of patterning within the organoids, the lineage relationships during organoid formation and the transcriptional (bulk and single cell) profiles of individual cell types. We are also applying CRISPR-Cas9 gene editing to patient stem cell lines to test the capacity of organoids to model human kidney disease. Finally, the use of fluorescent reporter lines is facilitating real-time imaging after in vivo transplantation to assess the degree to which we can mature such stem cell-derived tissue for renal replacement.

Host name: Dr Nicholas Hamilton
Host phone number: 62033
Host email: n.hamilton@imb.uq.edu.au

Seminars | This Week

IMB Chemistry and Structural Biology Division Seminar

Date/Time: Thursday 28th June 2018 12:30

Location: Seminar Room 3.142, QBP Bldg 80, UQ St Lucia

Title of talk: How do small molecule bacterial antigens modulate mucosal T lymphocytes?
Speaker's name: Dr Weijun Xu
Speaker's organisation: Institute for Molecular Bioscience
Talk abstract: We have investigated how a small molecule antigen derived from bacteria activates mucosal associated invariant T cells. The antigen has a uracil tethered to a flexible ribityl substituent. Four hydroxyl groups in the ribityl engage with a protein (MR1) expressed on the surface of antigen presenting cells as well as with the T cell receptor (TCR). Using molecular modeling, molecular dynamics and crystal structures we identify how these hydroxyl groups influence both antigen binding and the protein-protein interaction between MR1 and TCR. We find a key intramolecular interaction within the antigen that controls antigen flexibility and the adaptive immune response.

Title of talk: Arachnid venoms for targeting parasitic worms and insects
Speaker's name: Dr Volker Herzig
Speaker's organisation: Institute for Molecular Bioscience
Talk abstract: We have been screening our diverse arachnid venom collection for components targeting parasitic worms and insects. In our parasitic worm screen, we have identified the polyamine Ag366 from an American tarantula that was toxic to the nematode Haemonchus contortus, a major parasite of Australian livestock industries. Interestingly, Ag366 was even more potent against the nematode species Brugia malayi, which is responsible for lymphatic filariasis in humans and can lead to characteristic "elephantiasis" symptoms of massively swollen limbs. We have studied structural homologs to Ag366 to obtain structure-activity data and we further investigated the potential molecular targets of Ag366. Our screens for insect toxicity have focused on orally-active venom components, as oral activity would be an important feature of a useful bio-insecticide candidate. Interestingly, we found that oral activity is much more common in arachnid venoms than anticipated.

Host name: Professor David Fairlie
Host email: d.fairlie@uq.edu.au

Seminars | This Week

QBI Neuroscience Seminar

Date/Time: Wednesday 27th June 2018 11:00

Location: QBI, Level 7 Auditorium

Title of talk: Using Human iPSC-derived Microglia and Chimeric Mouse Models to Study Alzheimer's Disease
Speaker's name: A/Professor Mathew Blurton-Jones
Speaker's organisation: Department of Neurobiology and Behavior and Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, USA
Talk abstract: Microglia are strongly implicated in both the genetics and pathogenesis of Alzheimer's Disease (AD). Yet, studies of human microglia have been hindered by the difficulty in obtaining these cells and the need to examine them either in vitro or within post-mortem specimens. This problem has been further highlighted by recent studies demonstrating that isolated human microglia undergo rapid transcriptional changes with in vitro culture. Thus, there is pressing need to develop new approaches to directly observe and examine human microglial function in vivo. To address this need, we hypothesized that transplantation of human iPSC-derived hematopoietic progenitor cells (HPCs) into the early postnatal brain of immune-deficient mice would result in differentiation of functional microglia that more accurately recapitulate in vivo human microglia biology. iPSC-derived HPCs were transplanted into P1 immunodeficient MITRG mice that express humanized versions of key cytokines that facilitate long-term survival and differentiation of human myeloid cells. Transplanted mice were aged for 2-6 months and then exposed to either intrinsic or extrinsic insults including peripheral LPS, laser cell ablation, or transgenic-mediated production of beta-amyloid plaques. Brains were then collected for analysis by immunohistochemistry and recovery of human microglia by FACs sorting. Robust engraftment of human cells that morphologically closely resemble microglia was observed throughout the brain and these cells stained for multiple microglia markers including P2RY12, Iba1, CD11b, Pu.1, and TMEM119. Furthermore, exposure to insults resulted in human microglial activation, proliferation, and/or migration to injury sites and pathology. In addition RNA sequencing of FACS-sorted human microglia recovered from the mouse brain revealed numerous changes in the microglial transcriptome in response to LPS and the adoption of a human 'in vivo-like' transcriptional profile following transplantation. Both histological and functional analyses show that transplantation of human HPCs into the early postnatal mouse brain results in robust engraftment of microglia which actively monitor the CNS and rapidly respond to insults or injury. Taken together these data suggest that this model can be used to advance our understanding of human microglial biology in the context of normal brain development, aging, and disease.

Host name: Deirdre Wilson
Host email: d.wilson5@uq.edu.au

Seminars | This Week

Genomics of Development and Disease (GDD) Seminar Series

Date/Time: Thursday 28th June 2018 11:00

Location: Large Seminar Room

Title of talk: Widespread associations between grey-matter structure and the human phenome
Speaker's name: Baptiste Couvy-Duchesne
Speaker's organisation: IMB, Visscher Group

Title of talk: top3a and ddx21 is essential for the expansion of the lymphatic vascular lineage from a limited progenitor pool
Speaker's name: Kazuhide Okuda
Speaker's organisation: IMB, Hogan Group

Host name: Meredith Redd
Host email: m.redd@imb.uq.edu.au