George Klein (1925-2016) R.I.P.

George Klein (1925-2016) R.I.P.

George Klein was a pioneering cancer researcher with a long and successful career. He passed away at the age of 91. He fled Nazi prosecution in World War II and resettled in Sweden 1947, and became one of the leading scientists in tumor biology. George Klein spent many years of his career working on Epstein-Barr Virus, lymphomas and other cancers. Complete obituary published in Nature.

Mapping out the regulatory code of the human genome using synthetic biology

Mapping out the regulatory code of the human genome using synthetic biology

Gene regulation is a complex process involving a wide range of molecular components and mechanisms. We know that enhancers regulate gene expression through binding of transcription factors. Grossman et al. published a comprehensive study of enhancers and transcription factors using a synthetic biology approach.  The authors used a technique called massively parallel reporter assay, which uses thousands of natural and synthetic promoters. Using the technique, the contribution of genetic motifs and chromatin states on enhancer activity was studied. Additive and interaction effects between transcription factors and enhancers were found and known interactions in the literature were reproduced. The study greatly extends the known biology of PPAR-γ (peroxisome proliferator-activated receptors) and their role in adipogenesis (formation of fat tissue).

This is an interesting study coming out of the lab of the well-known geneticist Eric S. Lander (spearheaded the human genome project, called evil genius by some).

Regulatory genetics resources

  • VISTA Enhancer Browser – experimentally validated human and mouse noncoding elements
  • Human enhancer atlas – annotation of enhancers in the human hg19 genome
  • Integrated human enhancer database – a centralized on-line repository of predicted enhancers derived from multiple human cell-lines
  • FANTOM5 – functional annotation of the mammalian genome
  • JASPAR – contains a curated, non-redundant set of profiles, derived from published collections of experimentally defined transcription factor binding sites for eukaryotes
The alligator genome: teasing out the evolutionary history of estrogen signaling

The alligator genome: teasing out the evolutionary history of estrogen signaling

All reptiles such as alligators have temperature-dependent sex-determination (sex of the embryo is only determined by the incubation temperature, and not by genetic differences as in mammals and birds).

Many early efforts in genome sequencing are far from perfect. Usually, the initial genome sequence is called draft, and is intended as a first analysis to understand genome architecture. Improved genome assemblies have much utility, for example offering the ability of broader and long-range comparisons as well as analysis of repeats (e.g., mobile elements).

Rice et al. have generated an improved genome assembly of the American alligator (Alligator mississippiensis). The authors generated 210 million paired-end reads with the Illumina HiSeq 2500 instrument, which were then assembled using Meraculous. The genome size became 2.16 Gb (size is ~67% of the human genome), and showed longer continuity than the previous assembly from 2015.

Comparisons with the chicken genome revealed conservation of the estrogen-signaling pathways, indicating an important role of estrogen signaling even in a species without sex chromosomes.

Alligator genome resources

The molecular response to protective malaria unravelled

The molecular response to protective malaria unravelled

Malaria is a mosquito-borne sickness caused by unicellular eukaryotic parasites of the family Plasmodium. Malaria causes most damage in developing countries, where it can be fatal. World Health Organization estimated the number of Malaria cases in 2014 to more than 200 million. Symptoms of Malaria include fever, vomiting, headache, and fatigue. The malaria parasite has an intricate lifecycle, with several different stages in the mosquito and the host. The complicated life cycle is a reason why development of a vaccine is difficult.

Source: Wikipedia

A new study published in PNAS investigated the promising Malaria-vaccine candidate RTS,S (no, it is not a typo). RTS,S induces an antibody response, which is only partially protective due its inability to induce cytotoxic T cells. The efficacy of RTS,S is ~50%, which is the best we have at the moment for a malaria vaccine, but not good enough in general. 46 human individuals were enrolled in the study, these were then split into two groups that were given two different types of RTS,S. Both types had similar efficacy, although their immunogenicity signatures were not identical. Thus, the study highlights protective immunity through two distinct immunological mechanisms, and identifies new biomarkers that can be used to confirm protective immunity against malaria.

Proliferation of university administrators and rise of the underpaid adjunct professorship

Proliferation of university administrators and rise of the underpaid adjunct professorship

We usually don’t dwell in politics, thinking there are more important matters in life, such as the mysteries of genetics and biology. However, everyday life is an exposure to politics and policies. The Fall of the Faculty is the title of a new book by Benjamin Ginsberg and it targets the inequalities of the American higher educational system. Today only 17% of university instructors are tenured, meaning that most teaching is conducted by low-paid adjunct professors. From 1975 to 2011 the number of adjunct professors increased with 400%. The university feudal system works like this: at the top of the pyramid are tenured professors and administrator – these guys have generous pay and benefits. At the bottom you have adjunct professors, with no job security and low pay. Since 1975, endowment of top universities has increased steadily. However, has this led to an increase in the amount of tenured faculty per student? Apparently not. Universities have instead focused on hiring armies of administrators, deans, vice deans, provosts, and financial officers, who have proliferated at the expense of permanent faculty. This book is a critical and entertaining read for everyone who has been in academia.