2016 Research Week

RESEARCH WEEK 2016 TABLE OF CONTENTS ADMINISTRATION RESEARCH COMMITTEES ACTIVITY SCHEDULE LETTERS OF ENDORSEMENT GENERAL SESSION FACULTY, STAFF, AND STUDENT POSTER PRESENTATIONS FACULTY AND STUDENT ORAL PRESENTATION

On the Reaction Diffusion Master Equation in the Microscopic Limit

Stochastic modeling of reaction-diffusion kinetics has emerged as a powerful theoretical tool in the study of biochemical reaction networks. Two frequently employed models are the particle-tracking Smoluchowski framework and the on-lattice Reaction-Diffusion Master Equation (RDME) framework. As the mesh size goes from coarse to fine, the RDME initially becomes more accurate. However, recent developments have shown that it will become increasingly inaccurate compared to the Smoluchowski model as the lattice spacing becomes very fine. In this paper we give a new, general and simple argument for why the RDME breaks down. Our analysis reveals a hard limit on the voxel size for which no local RDME can agree with the Smoluchowski model

New Genomic Structure for Prostate Cancer Specific Gene PCA3 within BMCC1: Implications for Prostate Cancer Detection and Progression

The prostate cancer antigen 3 (PCA3/DD3) gene is a highly specific biomarker upregulated in prostate cancer (PCa). In order to understand the importance of PCA3 in PCa we investigated the organization and evolution of the PCA3 gene locus. METHODS/PRINCIPAL FINDINGS: We have employed cDNA synthesis, RTPCR and DNA sequencing to identify 4 new transcription start sites, 4 polyadenylation sites and 2 new differentially spliced exons in an extended form of PCA3. Primers designed from these novel PCA3 exons greatly improve RT-PCR based discrimination between PCa, PCa metastases and BPH specimens. Comparative genomic analyses demonstrated that PCA3 has only recently evolved in an anti-sense orientation within a second gene, BMCC1/PRUNE2. BMCC1 has been shown previously to interact with RhoA and RhoC, determinants of cellular transformation and metastasis, respectively. Using RT-PCR we demonstrated that the longer BMCC1-1 isoform - like PCA3 - is upregulated in PCa tissues and metastases and in PCa cell lines. Furthermore PCA3 and BMCC1-1 levels are responsive to dihydrotestosterone treatment. CONCLUSIONS/SIGNIFICANCE: Upregulation of two new PCA3 isoforms in PCa tissues improves discrimination between PCa and BPH. The functional relevance of this specificity is now of particular interest given PCA3's overlapping association with a second gene BMCC1, a regulator of Rho signalling. Upregulation of PCA3 and BMCC1 in PCa has potential for improved diagnosis

Amino acid-dependent cMyc expression is essential for NK cell metabolic and functional responses in mice

Natural killer (NK) cells are lymphocytes with important anti-tumour functions. Cytokine activation of NK cell glycolysis and oxidative phosphorylation (OXPHOS) are essential for robust NK cell responses. However, the mechanisms leading to this metabolic phenotype are unclear. Here we show that the transcription factor cMyc is essential for IL-2/IL-12-induced metabolic and functional responses in mice. cMyc protein levels are acutely regulated by amino acids; cMyc protein is lost rapidly when glutamine is withdrawn or when system L-amino acid transport is blocked. We identify SLC7A5 as the predominant system L-amino acid transporter in activated NK cells. Unlike other lymphocyte subsets, glutaminolysis and the tricarboxylic acid cycle do not sustain OXPHOS in activated NK cells. Glutamine withdrawal, but not the inhibition of glutaminolysis, results in the loss of cMyc protein, reduced cell growth and impaired NK cell responses. These data identify an essential role for amino acid-controlled cMyc for NK cell metabolism and function

Generation of 3 spinocerebellar ataxia type 1 (SCA1) patient-derived induced pluripotent stem cell lines LUMCi002-A, B, and C and 2 unaffected sibling control induced pluripotent stem cell lines LUMCi003-A and B

Spinocerebellar ataxia type 1 (SCA1) is a hereditary neurodegenerative disease caused by a CAG repeat expansion in exon 8 of the ATXN1 gene. We generated induced pluripotent stem cells (hiPSCs) from a SCA1 patient and his non-affected sister by using non-integrating Sendai Viruses (SeV). The resulting hiPSCs are SeVfree, express pluripotency markers, display a normal karyotype, retain the mutation (length of the CAG repeat expansion in the ATXN1 gene) and are able to differentiate into the three germ layers in vitro

Feminist Reflections on the Scope of Labour Law: Domestic Work, Social Reproduction and Jurisdiction

Drawing on feminist labour law and political economy literature, I argue that it is crucial to interrogate the personal and territorial scope of labour. After discussing the “commodification” of care, global care chains, and body work, I claim that the territorial scope of labour law must be expanded beyond that nation state to include transnational processes. I use the idea of social reproduction both to illustrate and to examine some of the recurring regulatory dilemmas that plague labour markets. I argue that unpaid care and domestic work performed in the household, typically by women, troubles the personal scope of labour law. I use the example of this specific type of personal service relation to illustrate my claim that the jurisdiction of labour law is historical and contingent, rather than conceptual and universal. I conclude by identifying some of the implications of redrawing the territorial and personal scope of labour law in light of feminist understandings of social reproduction