ATMscience

My interests

I am generally interested in everything relating to quantitative cell biology and biophysics.
I have a keen interest in the cytoskeleton and especially in the microtubules. I am also captivated by the cytoplasm and its physical properties. I do not have a favorite organism, I have worked with multiple model organisms (yeast, plants, mammalian cells) as well as in vitro and with non-model organisms (spirostomum). My investigative method of choice is microscopy and I have spent thousands of hours doing all kinds of microscopy. 


I have a broad interest in multiple fundamental research topics
•    Understanding the roles and regulation of cytoskeleton organization and dynamics
•    Describing the physical properties of the cytoplasm and their regulation
•    Deciphering how the properties of the cytoplasm impact cellular functions

Fused-2.jpg

The cytoskeleton is formed by a network of filaments, assembled from soluble proteins. I am fascinated by the dynamic properties displayed by these filaments. These filaments, especially the microtubules, undergo phases of growth and shrinkage, switching stochastically from one to another. These properties are fundamental and intrinsic and have been reproduced in vitro for decades. Yet, they are regulated in cells by a myriad of different factors as well as by the properties of the environment. Understanding how a cell organizes its network of microtubules and regulates its dynamics locally, polymerizing it in a given region while depolymerizing it in another is a central question if we are to understand cellular architecture. My Ph.D. work was focused on understanding the role of one regulator of microtubule dynamics, the EB1 protein from Arabidopsis thaliana (Molines et al., 2018, Molines et al., 2020). EB1 from other eukaryotes (yeast, mammals, fly) has been extensively studied in cell and in vitro but the plant ortholog differs in sequence and has been less studied. My work showed that EB1 regulates microtubules network organization in Arabidopsis (Molines et al., 2018) and that its effects on microtubule dynamics in vitro differ from the mammalian one (Molines et al., 2020). 

Microtubules re-organization blue light treatment arabidopsis

Microtubule network reorganization upon blue light treatment in Arabidopsis thaliana epidermal hypocotyl cell.
Lindeboom et al., 2013, Science.

Model of the Bacterial Cytoplasm.
McGuffee and Elcock, 2010, PLoS Comput Biol 

The cytoplasm is a complex environment. It is made of proteins, carbohydrates, nucleic acid, and ions, at a high concentration. It is a crowded and viscous environment in which proteins are in very close contact.  It is also a dynamic environment in which energy is permanently consumed to generate molecular motion. These properties are emergent from the composition of the cytoplasm, higher concentrations leading to higher crowding and viscosity. However, we do not understand its properties enough to predict how its composition influences its properties. It is also unclear if cells have evolved molecular mechanisms dedicated to detecting changes in cytoplasmic viscosity or crowding and rectifying them or if the cytoplasmic properties are passively regulated. Part of my postdoctoral studies have been dedicated to getting a better understanding of the physical properties of the cytoplasm in fission yeast (Garner, Molines at al., 2022). 

The properties of the cytoplasm are a fundamental aspect of cellular biology. Indeed, viscosity and crowding are bulk properties of a solution that are known to influence the various reactions that can happen in the solution. For example, in vitro, enzymatic reactions tend to be slowed down by an increase in viscosity and sped up by an increase in crowding. It is then evident that the metabolic reaction that happens in the cytoplasm could be sensitive to its properties. However, we do not know which reactions are affected or not or by how much. Part of that missing knowledge comes from the fact that the actual properties of the cytoplasm are not well described and also from the fact that it is hard to manipulate cytoplasmic properties in cells. My main postdoctoral study focused on using osmotic shocks as a way to acutely affect cytoplasmic properties which led us to show that microtubule dynamics is sensitive to the viscosity of the cytoplasm in eukaryotes (yeast, mammals and plants) (Molines et al., 2022). 

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Potential effect of crowding on proteins behavior.
From Kuznetsova et al., 2014