Understanding how the taxanes antitumoral drugs modulate cell microtubules

Researchers have found that addition of paclitaxel (a type of antitumoral drug) to microtubules alters their structure. This compound modulates the material properties of microtubules by converting destabilized growing microtubule ends into regions resistant to depolymerisation, eventually leading to cell death. Results were obtained at the NCD beamline of the ALBA Synchrotron.

Paclitaxel, one of the most commonly used antitumoural drugs, modulates microtubules, the biopolymers responsible for many essential cellular functions including cell division, movement and intracellular transport. This kind of drugs target tubulin subunits, the main microtubule proteins, and interfere with their dynamics, which can have the effect of stopping a cell cycle and can lead to programmed cell death or apoptosis.

Read more on the ALBA website 

Image: Microtubule X-ray fiber difractogram in presence of Paclitaxel.

Credit: NCD-SWEET beamline at ALBA Synchrotron

Winning the fight against influenza

Annual influenza epidemics and episodic pandemics continue to cause widespread illness and mortality. The World Health Organization estimates that annual influenza epidemics cause around 3–5 million cases of severe illness and up to 650,000 deaths worldwide. Seasonal influenza vaccination still remains the best strategy to prevent infection, but the vaccines that are available now offer a very limited breadth of protection. Human broadly neutralizing antibodies (bnAbs) that bind to the hemagglutinin (HA) stem region provide hope for a universal vaccine (Figure 1a)1,2. Binding of these bnAbs prevents the pH-induced conformational changes that are required for viral fusion in the endosomal compartments of target cells in the respiratory tract and, hence, viral entry in our cells.

>Read more on the SSRL at SLAC website

Image: Complex of Influenza virus HA with (a) Fab CR6261, (b) llama single domain antibody SD36, and (c) JNJ4796.

Clear view of “Robo” neuronal receptor opens door for new cancer drugs

During brain development, billions of neuron nerve cells must find accurate pathways in the brain in order to form trillions of neuronal circuits enabling us to enjoy cognitive, sensory and emotional wellbeing.

To achieve this remarkable precision, migrating neurons use special protein receptors that sense the environment around them and guide the way so these neurons stay on the right path. In a new study published in Cell, researchers from Bar-Ilan University and Tel Aviv University in Israel, EMBL Grenoble in France and University of Exeter in the UK report on their discovery of the intricate molecular mechanism that allows a key guidance receptor, “Robo”, to react to signals in its environment.

One of the most important protein signaling systems that guide neurons consists of the cell surface receptor “Robo” and its external guidance cue, “Slit”. “Slit and Robo can be identified in virtually all animals with a nervous system, from a 1 mm-long nematode all the way to humans,” explains researcher Yarden Opatowsky, associate professor and head of the Laboratory of Structural Biology at Bar-Ilan University and who led the research.

>Read more on the European Synchrotron website

Image: A surface representation of the crystal structure of the extracellular portion of human Robo2. The yellow region represents the domain where dimerisation takes place. Here, we see it blocked by the other domains, meaning dimerisation cannot take place and that Robo2 is inactivated.
Credit: Y. Opatowsky.

Revealing the path of a metallodrug in a breast cancer cell

Some types of cancer cannot be treated with classical chemotherapy. Scientists from Inserm, CNRS, Sorbonne University, PSL university, University Grenoble Alpes and ESRF, the European Synchrotron, are working on a metallorganic molecule as an antitumor drug. Their research has given thorough insights into its mechanism in attacking cancer cells. This study is published in Angewandte Chemie.

Triple-negative breast cancer, which represents 10-20% of breast cancers, is not fuelled by hormones. In fact, it tests negative for estrogen and progesterone receptors and excess HER2 protein. This means that it does not respond to hormonal therapy and antibody medicines. Given that it is more aggressive and often has a higher grade than other types of breast cancer, the scientific community is relentlessly trying to find a treatment.

>Read more on the ESRF website

Image: X-ray fluorescence maps of potassium, an essential physiological element of the cell (K, in pink), and, osmium a constitutive element of the metallocifen (Os, in green), in hormone-independent breast cancer cells exposed to the osmocenyl-tamoxifen derivatives.
Credit: Sylvain Bohic.