Varnesh Tiku

Genentech · Department of Infectious Disease

Acinetobacter baumannii is a clinically important, predominantly health care–associated gram-negative bacterium with high rates of emerging resistance worldwide. Given the urgent need for novel antibacterial therapies against A. baumannii , we focused on inhibiting lipoprotein biosynthesis, a pathway that is essential for envelope biogenesis in gra...

Mitochondria are pivotal organelles in the cell that regulate a myriad of cellular functions, which eventually govern cellular physiology and homeostasis. Intriguingly, microbial infection is known to trigger morphological and functional alterations of mitochondria. In fact, a number of bacteria and viruses have been reported to hijack mitochondria...

Acinetobacter baumannii is a highly pathogenic Gram-negative bacterium that causes severe infections with very high fatality rates. A. baumannii infection triggers innate as well as adaptive immunity, however, our understanding of the inflammatory factors secreted by A. baumannii that alarm the immune system remains limited. In this study, we repor...

Acinetobacter baumannii is a highly antibiotic-resistant bacterial pathogen known to cause severe life-threatening infections, including pneumonia, meningitis, and sepsis. Recent emergence of this bacterium as a serious nosocomial pathogen has led to categorization of A. baumannii as a "high-priority" pathogen by the World Health Organization (WHO)...

All Gram-negative bacteria produce outer membrane vesicles (OMVs) which are minute spherical structures emanating from the bacterial outer membrane. OMVs are primarily enriched in lipopolysaccharide (LPS) and phospholipids, as well as outer membrane and periplasmic proteins. Recent research has provided convincing evidence for their role in multipl...

Acinetobacter baumannii is a highly antibiotic resistant Gram-negative bacterium that causes life-threatening infections in humans with a very high mortality rate. A. baumannii is an extracellular pathogen with poorly understood virulence mechanisms. Here we report that A. baumannii employs the release of outer membrane vesicles (OMVs) containing t...

Mitochondria have a central role in regulating a range of cellular activities and host responses upon bacterial infection. Multiple pathogens affect mitochondria dynamics and functions to influence their intracellular survival or evade host immunity. On the other side, major host responses elicited against infections are directly dependent on mitoc...

Ubiquitin and ubiquitin-like proteins (UBLs) are essential regulators of a multitude of cellular processes, including autophagy. It is known that these proteins relay their effects by covalently modifying their substrate molecules. As an exception to this norm, Pang et al. report a novel phenomenon in which the UBL ATG12 interacts with its substrat...

Innate immunity is the first line of defense against infections. Pathways regulating innate responses can also modulate other processes, including stress resistance and longevity. Increasing evidence suggests a role for the nucleolus in regulating cellular processes implicated in health and disease. Here we show the highly conserved nucleolar prote...

The nucleolus is a prominent membraneless organelle residing within the nucleus. The nucleolus has been regarded as a housekeeping structure mainly known for its role in ribosomal RNA (rRNA) production and ribosome assembly. However, accumulating evidence has revealed its functions in numerous cellular processes that control organismal physiology,...

Animal lifespan is regulated by conserved metabolic signalling pathways and specific transcription factors, but whether these pathways affect common downstream mechanisms remains largely elusive. Here we show that NCL-1/TRIM2/Brat tumour suppressor extends lifespan and limits nucleolar size in the major C. elegans longevity pathways, as part of a c...

List of organisms in which FoxJ1 orthologs were searched using the full-length human FoxJ1 protein sequence. (XLSX)

List of organisms in which FoxJ1 could not be identified either by reverse BLAST or phylogenetic analyses. (XLSX)

Normal motility in wild-type and foxJ1-1(RNAi) worms compared to the inchworming gait observed in worms with foxJ1-4(RNAi) and ift172(RNAi). (MOV)

Expression levels of invertebrate FoxJ1 proteins in zebrafish embryos. Western blot showing roughly equivalent levels of the zebrafish and sea urchin FoxJ1 proteins, but lower levels of expression of placozoan FoxJ1. Tubulin levels were measured as loading control. (JPG)

It is generally believed that the last eukaryotic common ancestor (LECA) was a unicellular organism with motile cilia. In the vertebrates, the winged-helix transcription factor FoxJ1 functions as the master regulator of motile cilia biogenesis. Despite the antiquity of cilia, their highly conserved structure, and their mechanism of motility, the ev...