03-02-2023. Congratulations to the Yu lab for their publication, Efficient end-to-end learning for cell segmentation with machine generated weak annotations. The article focuses on cell segmentation models trained with weak annotations that can be programmably or semi-programmably produced from experimental data. It provides an efficient means of performing single-cell segmentation for microscopy image analysis.

03-01-23. The Guertin lab characterized the normal physiological role of the protein ANKLE1 in red blood cell development and how increased expression of Ankle1 leads to an increased risk of developing breast cancer.

Background: GWAS analyses have identified thousands of regions associated with physiological phenotypes and disease risk phenotypes. Integrative GWAS and eQTL analyses can often hone in on the candidate causal genes within the region by looking for colocalization of GWAS and eQTL variants. The genotyping revolution allows geneticists to keep identifying more associated loci with smaller and smaller effect sizes, but characterizing the causal genes and mechanisms by which the genes manifest as organismal phenotypes lags substantially behind. The chr19p13.1 locus was first identified over 10 years ago as a locus that contributes to the risk of breast and ovarian cancer. The wrong genes were thought to be the causal genes for over six years, but integration with eQTL analysis repeatedly and convincingly pointed to ANKLE1 as the causal gene. There are only a handful of rigorous publications that have explored the molecular, cellular, and physiological functions of ANKLE1, but none of these studies explore the role of ANKLE1 in breast cancer biology. ANKLE1 is primarily expressed in hematopoietic tissues of vertebrates, but ANKLE1-deficient mice are viable without any detectable phenotype in hematopoiesis.

This latest work finds that the developmental role of ANKLE1 is to cleave the mitochondrial genome during erythropoiesis. Drs. Przanowski and Guertin also determined how ectopic expression of ANKLE1 confers breast cancer risk. The publication in Communications Biology reports that ectopic expression of ANKLE1 in breast epithelial spheroids cleaves mitochondrial DNA to induce mitophagy and trigger a shift in metabolism to glycolysis. These metabolic changes cause resistance to apoptosis in TP53 negative cells. Two recent GWASs quantified mitochondria DNA abundance and found that genetic variants with the ANKLE1 locus contribute to mitochondrial DNA abundance. This publication provides a direct mechanistic link between the overlapping GWAS signal for breast cancer risk and mitochondrial DNA copy number.

03-01-2023. Congratulations to Ann Cowan, Peter Setlow, and other collaborators for their work on Bacillus subtilis. The article, entitled Expression of the 2Duf protein in wild-type Bacillus subtilis spores stabilizes inner membrane proteins and increases spore resistance to wet heat and hydrogen peroxide looks at sporulation in B. subtilis and used VCell modeling to analyze the characteristics of the spore membrane in cells with mutations in genes related to germination.

11-11-22. Congratulations to Corey on his recent collaborative publication, Voltage imaging reveals the dynamic electrical signatures of human breast cancer cells Commun Biol. 2022 Nov 11;5(1):1178. doi: 10.1038/s42003-022-04077-2. Peter Quicke, Yilin Sun, Mar Arias-Garcia, Melina Beykou, Corey D Acker, Mustafa Djamgoz, Chris Bakal, Amanda J Foust. Recent studies at the Imperial College London and The Institute of Cancer Research, London uncovered large voltage fluctuations in breast cancer cells. Remarkably, these voltage fluctuations resemble very slow, upside-down versions of action potentials, which are electrical signals inherent in brain and heart cells. Voltage-sensitive dyes were provided by UConn’s start-up company Potentiometric Probes and Dr. Acker assisted with imaging methods, including ratiometric voltage imaging, to detect the voltage fluctuations reliably. The underlying mechanisms and role that these fluctuations might play in cells transitioning to being cancerous are intriguing open questions and avenues of future research.

Please read Imperial College London’s article on this new discovery, “Scientists uncover potential ‘electrical language’ of breast cancer cells“.

12-06-22. Congratulations to Ann on her recent publication, Liu, Y., E.M. Bafaro, A.E. Cowan, and R.E. Dempski. 2022. The transmembrane domains mediate oligomerization of the human ZIP4 transporter in vivo. Sci Rep. 12:21083. The work used Fluorescence Correlation Spectroscopy (FCS), performed in CCAM,  to determine the oligomerization state of wild-type or mutant zinc transporter protein ZIP4 in the plasma membrane.