Dissecting the fundamentals of transcriptional regulation

Aïsha​ ​Mientjes



Seminar 7:​    

Speaker:​ ​Martin Howard

Department:​ John Innes Center

Subject:​ Dissecting the fundamentals of transcriptional regulation

Location:​ ​TU​ ​Delft

Date:​ 12-01-2018


On the 12th of January, there was a bionanoscience seminar given by Martin Howard. He was trained as a physicist, but he has since then moved into the field of biology as currently does research on epigenetic memory.

The presentation was started of by the question: when is transcription regulated in an on/off manner and when is it regulated in a continuous manner? In addition he asked whether the process is noisy/bursty or not. The rest of the seminar mainly concerned itself with the first question, because there was too little time to go into the second question.

Epigenetic inheritance means the inheritance of phenotype not based on the DNA sequence. Martin Howard studies epigenetics by zooming in on one locus. The system that he studies is called Arabidopsis, in particular flowering locus C (FLC). This locus is involved with aligning plant development with the seasons. The switch to flowering in a plant is repressed by FLC. FLC is in turn repressed by vernalization.


The level of FLC throughout the year.


Correct timing is very important for the FLC is very important because plants cannot flower too early or too late. In the graph above it is visible that the level of expression on return to the warm period depends on the length of the cold period. The Arabidopsis model is very slow, which can be difficult in experiments but also allows a very quantitative study.


After an explanation of the model, the speaker went on to explain about epigenetic memory. This memory can be stored in a trans way and in a cis way. Trans means that it is stored in diffusible factors and is uniformly distributed, cis means that it is stored in chromatin based histone modifications and is locally stored. There is still an active debate in biology as to how the memory is stored.


Systems for digital cell autonomous epigenetic memory is bi-stable. For an individual cell, it is all or nothing. With this knowledge, it can be concluded that the quantitative quality (shown in the graph above) must come from the fraction of cells. The final part of the presentation concerned an experiment with which Martin Howard showed that there is a favour for the cis memory.


I found this seminar very interesting because it largely concerned ecology, a subject which is not often discussed during these seminars. I found the model quite interesting and it was nice to hear that a lot of field research was done for the discussed experiments as well. The final part of the presentation was quite difficult to understand but the rest was fairly easy to follow in my opinion. In addition, I liked that Martin Howard has a very ‘physicist’ way to explore biology, he focussed on a single locus which made it quite easy to explain epigenetics.


A paradoxical human mesh

Fibrin clots at work in forming a mesh of blood cells to fill up a hole in a vessel.

(Eye of Science / Photo Researchers, Inc)

Written by Raman van Wee

Speaker:  Gijsje Koenderink

Department: FOM institute AMOLF

Subject: Biophysics of fibrin clots     

Location: Erasmus MC         

Date: 18-12-2017   

 Professor Koenderink kicked off with a great description of her as hardcore physicist meeting the biologists in the middle: mechanics of fibrin clots. This was a nice reminder of the value of Nanobiology by means of bridging this gap. Her seminar lasted for roughly half an hour and was very understandable, as Koenderink undeliberately continued perfectly on our knowledge gained in Biophysics and Thermodynamics and Transport.


The topic of her talk was the: “Biophysics of fibrin clots” and more specifically the mechanical characteristics of fibrin clots. Unlike many synthetic materials fibrin shows both stiffness as well as great elasticity. This results in a tissue that on the one hand doesn’t easily deform when put under stress and on the other hand doesn’t break when put under great force. This in line with the function of fibrin clots: serving as a band aid when the body is at risk of blood loss. The clots should withstand both the mechanical pulling and pushing force of moving cells and the bloodstream putting stress on it. Not only the tissue as a whole, but also individual cells showed these characteristics. By using a number of techniques including an optical tweezer she was able to stretch a single fibrin polymer, in this case by using lasers. Having measured the applied force and the stretch, the stiffness could be determined.

Another technique that was used was shear rheology, which makes use of displacement of two parallel plates with fibrin that interconnects them. By shifting the plates and measuring the resistance, the shear/stress ratio could be measured, being yet another typical characteristic for a material. A contrast worth noting between her research and most research done in Rotterdam was that at AMOLF the research was much more quantitative.


All in all fibrin is an extremely effective protein that supports wound healing. It is both stiff and elastic, explaining the title. Fibrin is better able to restore its original state if it stretched quickly rather than when it is stretched slowly. At last fibrin shows a stiffer behavior when first being compressed to then later be stretched.




“Biophysical properties of fibrin”


Speaker:             Gijsje Koenderink  
Department:     Biological Soft Matter
Subject:              Biophysical properties of fibrin
Location:           Rotterdam, Wytemaweg 80 
Date:                    18-12-2017
Author:               Maricke Angenent


Gijsje Koenderink is the group leader of the research group ‘Biological Soft Matter’ at AMOLF, one of the Dutch research laboratories. Her group is mostly interested in the physical mechanisms behind self-organisation and the mechanical properties of the cytoskeleton. She explained that research is performed in two main areas. One of those is the cellular approach, in which a minimal cell is constituted with the help of cytoskeleton proteins that show a high level of self-assembly. This so-called minimal cell can then be used to examine all sorts of physical properties individually. The other approach is on the level of tissues. Living cells are brought into extracellular matrices that resemble the biological tissue environment. As a result you can analyse how cells respond to specific factors in the environment and thereby determine sensory mechanisms of the cell. In this presentation Gijsje used the subject of fibrin fibres and their biophysical properties to exemplify the current methods and approaches used in her lab.

Fibrin is a protein that is involved in blood clotting. You can imagine that this particular protein must be mechanically very stable, as you do not want any premature rupture of the fibrin complexes resulting in unwanted bleeding. Mechanical stability requires that a protein can withstand rather large forces without its overall structure being changed. In case of the fibrin proteins this stability was tested by using a polymerized fibrinogen protein (fibrinogen circulates in the blood stream and is enzymatically turned into fibrin fibres in case of injury, causing blood clotting), which was glued to one of two plates. Subsequently the other plate would be moved in such a way that the fibrinogen protein was stretched to several times its own length. From this experiment it was observed that a fibrin network is initially very random, however once stretched the various fibrin fibres are aligned into a more ordered structure. Gijsje even hypothesized that the lengthening of the fibres not only happens due to the straight alignment, but that the proteins itself might be stretched as well!

A different method used to determine the degree of stretching, was shear rheology. This technique utilizes a round plate on which the material to be examined can be deposited. A second plate is put on top of this round plate such that the protein you are analysing is enclosed between the two plates. Thereafter you can move the plates in order to apply (known) forces to the protein. From the results of this experiment and corresponding graphs, the elastic modulus of the fibrin fibres was determined. The elastic modulus can be understood as the relation between the deformation and stretch of a material. The conclusion was that the more fibrin is stretched (=more deformation) the stiffer the fibrin clots become. One explanation for this was that a relaxed fibrin fibre can be assumed to be a “floppy protein”. Once this floppy protein is stretched further it gets increasingly difficult to increase the stretch even more, thus leading to more stiffness.

Logically, the next step in the experiment was to question why fibrin is stretchy. Somehow the internal structure of fibrin fibres must be stretched, however with the previous assays you do not see what is going on internally. Therefore yet another approach had to be taken. The optical tweezers were introduced, which allow you to perform measurements on one single fibre at the time. Optical tweezers make it possible to hold very tiny particles, like single molecules, between two beads and then move them around by applying forces in any direction. In Gijsjes experiment, a single fibrin fibre was glued to both of the beads of the tweezer and then pulled apart. So now you are actually stretching a single fibre and thus you can determine the elastic modulus of a single fibrin instead of the modulus from the entire network, as was done before.

optical tweezers
Figure 1:  Optical tweezers. Protein stuck to two beads. One is kept in the same position, the other is moved to introduce stretch.

It is clear now that fibrins stretch on the single cell level in addition to the stretching caused by the alignment of cells. Most probably this molecular stretching originates from molecular unfolding of the protein. When coiled coil regions unfold due to induced conformational changes, you can expect lengthening. This lengthening can explain why a single fibre can stretch under certain conditions.

A final remark was that fibrin clots get stronger after they have been compressed. During the process of compression the clots are actually softened, however once you bring the material back to the decompressed state you see that the network has become stiffer than before. The tested hypothesis was that during compression water is pushed out of the fibrous network. Consequently the fibres are brought closer together which allows them to make new (irreversible) bonds. Once the fibres are then decompressed you actually stretch the new bonds which stiffens the fibre network. Double optical tweezer were used to verify this hypothesis.

So with the help of various laboratory set-ups, more and more is known about the biophysical properties of fibrin. Once the stretching and mechanical strength of fibrin clots is fully understood we can start to think of various clinical applications. For example, the gained knowledge can be used in thrombosis treatments or the biophysical properties can be used to increase mechanical stability of mutated fibrin variants. I think Gijsje presented us with an interesting seminar. I had not expected that the topic would be very relevant to us as nanobiologists, but it turned out that there was actually quite some overlap with topics from our curriculum.



Cell Biology of myelin

Speaker:                            Mikael Simons
Department:                    MPI Experimental Medicine, TU Munich/DZNE Munich
Subject:                             Cell Biology of myelin in the healthy, diseased and aging brain
Location:                           Rotterdam, Wytemaweg 80
Date:                                   02-11-2017
Author:                              Maricke Angenent


Myelin is one of the most abundant structures found in the nervous system. It has a sheath-like structure that seemingly envelopes nerve fibers, or so called axions, thereby providing an insulating and protecting coating to the axion. One of the well-known functions of myelin is to maximize the conduction velocity of axions. However that is not all, myelin also plays an important role in axonal transport and preventing axonal degeneration. The latter is what Mikael Simons is most interested in. His main goal is to understand the process of myelin formation and how myelin structures change during specific diseases. Once this understanding is established, you can start to think of applications such as introducing remyelation as a treatment for degenerative nerve diseases. The talk had a well-defined structure with three main topics. First up was the formation of myelin, followed by a theory of how myelin maintains axonal functioning and ending with myelin in the diseased and aging brain.


Myelin formation mainly occurs in the first year postnatally, but continues until the age of 20 or when the brain has reached the adult stage.  Oligodendrocytes are the cells which drive the formation of the axon wrapping. The precursors of those cells move to the correct location where they differentiate in the mature oligodendrocytes. Those mature cells can then interact with the central part of axons. The question posed was how the multilayered membrane structure of myelin is created, when it all starts from this one oligodendrocyte (a point source). To study this M. Simons and his colleagues used high pressure freezing to conserve the myelin structure in the best possible way. Previously, due to the compact structure with a high level of lipids, myelin samples were often damaged and thus difficult to analyze correctly. In addition, high resolution volume microscopy by ion beam milling was put into practice, to directly image the growing myelin sheaths. With these two advanced techniques, it was easy to identify growth profiles and convert this to models of how myelin structures are created. The conclusion was that there are actually two distinct growth movements. Firstly an inner loop wraps myelin sheaths around the axon, and secondly all of the layers slide latterly along the axon to the sides. Surprisingly, it was the inner layer where growth seems to be happening, despite the fact that actually membrane growth is initiated by the oligodendrocyte, which is located on the edge of the axon. This means that the newly produced membrane must be transported all the way to the inner loop. An explanation for this would be that the membrane is transported through cytoplasmic channels and then deposited on the inner layer of the myelin sheaths.

These cytoplasmic channels have another function as well. They are involved in maintaining axonal functioning. Since axons are isolated by myelin wrapping, their metabolism thus depends on the permeability of myelin sheaths. Energy sources needed for axonal processes, such as metabolites, are provided through the sheaths. This happens with the help of cytoplasmic channels within myelin, which connect the cell body and the inner most membranes to the environment. This is considered to be an important aspect of axonal maintenance.

In the next part of the seminar, Simons continued with an explanation of how the myelin membranes are compacted and what the effect of this compacting is on the functioning of axons. One of the proteins involved in this process is called myelin basic protein, ‘PLP’, which by self-interaction and polymerisation compacts the membranes. In the normal dispersed state, charges of opposite membranes repel. However in the presence of the polymerized protein, the charges are neutralized and the membranes can be compacted from the outer layer towards the inner layers. The second involved protein is CNP, which localizes cytoplasmic channels and keeps the cytosol within the membrane at this position. As a result CNP prevents that all the cytosol is being squeezed out and thus avoids over compaction of the membranes. In the experiments it became clear that CNP knockouts result in severe axonal degeneration. This indicates that if CNP is not present in the cell, the coupling of the myelin sheath to the axon (and thereby metabolite provision) is lost. So if CNP is not present, there are no cytoplasmic channels which means that no energy sources can be provided, resulting in axonal degeneration.

Finally, a few diseases were addressed involving axonal degeneration. The underlying mechanisms were discussed in some detail, but I found this part rather difficult to understand. The main point made was that macrophages and outfoldings of the myelin membranes (and accumulations of those in lysosomes) are among the main contributions to axonal degeneration. For me the last part of the presentation was a bit to detailed, but overall it was an interesting topic with a new take on myelin functioning.

Cell biology of myelin in the healthy, diseased and aging brain

Speaker: Mikael Simons
Department: Clinical Genetics
Subject: Cell biology of myelin in the healthy, diseased and aging brain
Location: Erasmus MC
Date: 02-11-2017
Author: Renée van der Winden

Today Mikael Simons came to talk to us about his research on myelin, the sheath that covers axons in nerve cells. He first explained a bit about the general structure and workings of myelin and then he moved on to discuss what happens to myelin during disease and aging.

A critical part of Simons’ research was to start fixating the axons by high pressure freezing instead of using chemical fixation. Chemical fixation does not work well on myelin, because it contains fatty molecules. Using this new method of fixating allowed Simons’ group to see details not seen before in myelin.

Myelin is made by cells called oligodendrocytes. When myelin is being formed, it grows in two directions. The inner layer that is directly on top of the axon drives growth and moves in a spiral-like manner, so that the myelin sheath thickens. The outer layer of myelin moves sideways, so that the entire length of the axon is covered. One of the research questions that Simons had, was what the driving force of the inner layer (also called the inner tongue) is. It turns out this is actin, which is only present at this site during growth. Another question was how myelin maintains axonal function. At least one of the reasons for this turned out to be that oligodendrocytes convert glucose into lactate, which is used as an energy source by axons. However, this leads us to another question: How can lactate get through the myelin to reach the axons? Simons found out that this happens through so-called cytoplasmic channels. The layers of myelin are held together by a protein called myelin base protein (MBP). At certain locations another protein, CNP, intervenes to keep the layers open, thus forming channels through the myelin.

image descriptionFigure 1: Schematic overview of myelin growth and cytoplasmic channels (Simons et al., 2014)

To research what happens to myelin during disease, Simons’ group mimicked two diseases, MS and NMO. In these disease myelin is damaged. Simons was particularly interested to see what myelin looks like when it is broken down. They found out that during NMO the inner tongue vesiculates first and the vesiculation then spreads through the myelin. In MS there is usually more splitting of the myelin sheath and also bulging out of the sheath. The hypothesis for the breakdown mechanism is that MBP dissociates, causing the myelin to fall apart. This turns out to be true in culture, but has yet to be shown to be true in vivo.

Lastly, Simons talked briefly about myelin in relation to aging. It turns out that there are more microglia and more lysosomes with age. The hypothesis was therefore that microglia clear myelin during aging. This hypothesis is supported by the fact that it was sometimes possible to observe myelin fragments in microglia.

All in all I thought this seminar was easy to follow and I thought it was quite interesting. I am interested in neuroscience as a whole, so I always like to follow seminars that are related to it.

How to achieve cellular replication without fail: lessons from bacterial cells

Speaker:             Christine Jacobs-Wagner
Department:     Microbial sciences institute, dept. of molecular cellular and developmental biology
Subject:              How to achieve cellular replication without fail: lessons from bacterial cells
Location:            TU Delft, BN-seminar
Date:                    13-10-2017
Author:               Maricke Angenent

 A cell partitioning mechanism which does not involve any of the complicated processes such as cytoskeleton filament assembly, motor protein functioning and the participation of the actin proteins. That is a system we were introduced to by Christine Jacobs-Wagner, who is currently the principle investigator in the Jacobs-Wagner lab at the university of Yale. She started her seminar by giving a short outline on cell replication in general. Hereafter the presentation would consist of two distinct parts. Firstly the focus was on how to ensure that partition of cell compartments happens equally among daughter cells. The second part was supposed to be about how different processes are integrated, especially how the cell cycle function integrates cell metabolism. The latter topic would have been rather innovative as the cell cycle and metabolism are usually viewed separately. Unfortunately an hour proved too short to cover both of the subjects, so instead Christine set on answering some additional questions on the first subject.


Christine started by emphasizing the fact that replication is a truly remarkable process. As she said “the ability to replicate distinguishes the non-living organisms from the living”, which is the source of her fascination for the process. In her lab, bacterial replication in particular is analyzed, since replication is fast and it is an incredibly robust processes. Replication is a stochastic process, meaning that it is submissive to internal variations, yet the process seems to never fail. One of the proposed reasons for this observation is that various processes are highly integrated and often rely on intracellular organization. But how exactly is this spatial organization achieved?


Though diffusion is an effective means of molecular transport in bacteria, due to travel distances being small, this only leads to random distributions. This in  itself is not a problem, however when you have a low copy number, the probability of finding all copies of a cellular compartment on one side of the cell considerably increases. Consequently, the chance to obtain unequal daughter cells also rises. Diffusion in bacteria is thus ineffective for partitioning cellular compartments in low count. A different separation machinery must be present in bacteria to partition single components. As Christine explained, this mechanism makes use of stochastic interactions that are transformed into active transport, which results in the spatial patterning of low count cell compartments. Based on experiments, it was concluded that when you have more than one copy in the cell, they are equidistantly distributed among the axis of the cell ensuring their propagation to the daughter cells. This distribution was analyzed for the plasmid system, as this system is best understood compared to others.

In this experiment, the mechanism of just a single plasmid was taken into account rather than of a cluster of plasmids, which you would normally encounter in real situations. Two proteins are of central importance in the partitioning mechanism: parA and par B. The former mediates active transport and binds to the chromosomal DNA  as a dimer. The latter binds to a specific sequence of a plasmid, resulting in a plasmid rich region (or so called cargo). Bound parA interacts with the parB cargo, resulting in the oscillation of a single plasmid cluster over the nucleoid. What is interesting, is that parA does not form any cytoskeleton filaments, nor does it use any motor proteins, yet the oscillations point to a form of active transport. In modeling this process it is important to assume that chromosomal DNA is not static. Instead the DNA (and thus also when parA is bound) experiences intrinsic fluctuations, which is observed as “wiggling”. Now the plasmid cargo (=parB) diffuses until it encounters parA, where it activates hydrolyzation. Consequently the parA is released from the DNA and parB can go on to interact with a different parA-DNA complex. When plotting the movement of parB over time, you obtain evidence for oscillatory behavior, where the plasmid goes from one end of the nucleoid to the other end of the nucleoid. This movement usually follows the direction of the parA gradient as the chance for interactions is higher in an environment with a higher concentration of bound parA.

seminar report 2The above figure shows the interaction of two parB plasmids, resulting in an opposite spatial organization.

In practice not just one, but multiple plasmid cargo’s are present in the cell. All of them undergoing interactions with the DNA-bound parA. These cargo’s influence each other’s direction because as they get closer the surrounding will be depleted of parA making sure that the cargo’s will turn around to go to a more favorable surrounding (where more parA is present). This influence happens continuously and as a result a regular pattern arises in which the cargoes are aligned along the axis of the bacteria. The regular patterning leads to correct partitioning of low counts during replication.


So in a nutshell, Christine introduced us to a replication mechanism, simpler and easier to generate than the conventional system. A mechanism in which there is no need for cytoskeletal structures or motor proteins since the DNA fulfills a mechanical function instead. Only two factors are needed, factor A binding the DNA and factor B ensuring the lifetime of binding of A. This simple mechanism relies on random fluctuations in the chromosomal DNA and stochastic interactions between various plasmids, which leads to a perfectly organized, spatial pattern. Overall I thought the seminar was fascinating, especially because I had never heard of this alternative partitioning machinery before. In addition, Christine incorporated many expressions which we have just covered in our lectures on physical biology of the cell, showing me how the theoretical information is also really applied nowadays in the laboratories.

Mechanotransduction in collective cell migration and its synthetic mimic

Speaker:             Joachim P. Spatz
Department:     Max Planck Institute for Medical Research, department of Biophysical      Chemistry, Heidelberg, Germany
Subject:              Sequential bottom-up assembly of synthetic cells
Location:            TU Delft, BN-seminar
Date:                    08-09-2017
Author:               Maricke Angenent


Joachim Spatz was the invited speaker of today’s seminar. He presented a talk which was organized in two main topics, starting with an introductory part on the self-organization of biological systems. This organization is also observed on cellular level and by making simulations of this process, the physical laws of collective cell migration can be studied in more detail. Subsequently, Spatz moved on to his most recent subject of research, which involves the field of synthetic biology. He elaborated on the progress his department has made on the creation of a synthetic cell and how this cell could be brought into a biological environment.


Collective cell migration
When comparing different forms of collective movement, whether it be on a macro or micro scale, you will find similarities no matter what the object is. One of those is that each system will find hierarchy at some point in the process. Since the similarities in collective migration were so striking, it was nothing but logical to set out for overlapping ‘rules’ involved in the behavior. This is what lead Spatz to his conducted experiments, which were mostly focused on the upper layer of skin, the epidermis. When you look from the top you can clearly see the dynamics of individual skin cells and how they are all mechanically interconnected. Consequently simulations allow for in depth analysis of how the movement is actually established. With special measurement techniques, forces on the various cells were measured, which were then used to calculate stresses between individual cells. The result obtained was that the force correlation length corresponds to the length of approximately 10 cells, meaning that the force exerted by one cell can influence the migration of other cells separated by maximally 9 others.

seminar report 1Fig 1. The forces involved in collective cell migration can be compared to rope pulling. The force is constantly passed to the adjacent cell, up to 10 cells further
Source: http://www.cell.com/trends/cell-biology/fulltext/S0962-8924(11)00127-9

The next experiment involved a confinement of cells. During the assay the cells were (at time t=0 ) allowed to spread to an area without any other cells. Interestingly, the result showed that even though cells are genetically identical, they do not move in the same direction nor at the similar speed. Now by combining the knowledge of before and by again computing the forces present, a so-called leader cell could be identified. A cell which is the first to move from the confined space and seemingly ‘pulls’ the other cells with him. Subsequently it was studied what the requirements were to become such a leader. To do so, the field looked at leader cells which had already appeared and then went back in time to study the prior forces and their particular location.

What I found surprising is that the system of cells always regulates back to the essential spacious organization with respect to the leader cells, even after being disrupted. Showing that it is indeed a very mechanically regulated system, including cells that collectively integrate forces together.

The synthetic cell
Overall I thought this part of the lecture was more difficult to understand than the first part, mostly because of quite some difficult terminology which I am not very familiar with, yet. Despite that it was very interesting to listen to, as it appeared to me as a promising approach to making an actual fully function cell. The main idea was that Spatz and his research group are now making synthetic cells by first stabilizing water droplets and then sequentially adding various essential cell compartments. To do so the water particle, which is a mechanically very strong template, is brought into an electric field causing the cell membrane to become more porous. Subsequently, pico-injection was utilized to inject quantified volumes into the ‘synthetic cell’.  What I picked up as most important message was that the sequential addition was of real importance for it allows to reach complexities which you could not reach if you try to make the entire cell in one go.

On a personal note, I thought the seminar was very fascinating and I learned a lot of new information. I was not acquainted with all the theories behind collective cell migration, and to be honest had never acknowledged it before. However it turns out to be a very regulated process with many physical laws to be discovered. For me the second part about making a synthetic cell was what really sparked my interest. I found it amazing to find out that the basic molecule they are using to make a synthetic cell is just an ordinary water molecule! I look forward to hearing more about this kind of recent innovations in the biological field and all of the possible applications.

Mechanotransduction in Collective Cell Migration and its Synthetic Mimic

Written by: Raman van Wee

Speaker:  Joachim P. Spatz

Department: Biophysical Chemistry

Subject: Mechanotransduction         

Location: Applied Sciences  

Date: 08-09-2017   



Spatz kicked off by showing us several videos of collective movement, both at the population level and at the cellular level. The latter included wound healing and formation of lateral line in zebrafish. Next a video of the motion of an epithelial monolayer of upper skin came by, it was very chaotic and movingly, which actually surprised me, I was expecting a rather static situation. Quantitively speaking groups of 10 cells up to 200 micrometer showed to behave as a collective, tuning the direction of the force to the group. In contrast there are leader cells, which go into a space on their own, followed up by the rest of the group. By reversing videos, behavior of leader cells could be investigated before it became apparent that the cell would become a leader cells. These cells seem to be predetermined, as they are at least 1000 micrometers apart of each other. The system regulates itself as shown by putting several leader cell too close to each other leading to the system eliminating those that are unwanted and thus leading to a stable, well distanced situation of leader cells. Remarkably if a group of followers, following a leader cell, threatens to exceed 10 followers, a new leader is brought forward from the group. I would say this requires extensive communication and coordination to execute well.

The second part of the seminar was about making a synthetic cell. This begins by making droplets having bilayer of membrane. Using sequential pico-injection microfluids, proteins and lipids could be inserted into the future cells. This sequential addition is very important, blending it all together at once doesn’t do it. Although once in the synthetic cell, the different components can not be separated with the eye, they do actually collaborate into larger structures. Interestingly, including myosine leads to the cell rotating around its axis. The need/strength for this rotating became clear when rotation was blocked by attaching a bead. In that case tension would build up until the cell would lose contact with the glass.

Afterwards we had the opportunity to speak to Spatz directly and ask him a few questions. We came to realization that he thinks in one year from now his synthetic cells will have some sort of mitochondria like energy factories. For the duplication part of life he thinks other research previously done can be very beneficial, drastically lowering the time required to integrate it in his cell. Besides, what actually surprised me was that his seminar was primarly based on 2 papers, whereas I expected more.



Collective migration is mechanically regulated by the length up to which cells collectively integrate forces together. The cells follow this rule to select and follow new leaders. In synthetic cells, components have to be inserted one by one although they eventually entangle. Forces in a cell can lead to the cell rotating around its axis.

Information of the structure of the universe

written by: Raman van Wee

Speaker:      Robbert Dijkgraaf

Department: Physics dept. Princeton

Subject:       The relation between the extremely large & the tiny world

Location:     Applied Sciences

Date: 07-09-2017   

Professor Dijkgraaf told us about the various scales scientists work at. We concluded that life (& Nanobiology) is centered at the middle of this sizescale.
According to Dijkgraaf this makes studying life extra challenging. In the outer sizes a different set of rules and equations hold, but in the middle, where life happens to be, the collide, making it extra hard. I found this both surprising and intriguing. Surprising because it posed quite a contradiction with my
instinctual beliefs, intuitionally I felt the center of scale is the relatively easy part and going out into space or into the world of quarks would be more challenging. It intrigued me as well, because as a Nanobiologist I am working right around this center!
The concepts in the introduction were well imaginable and thus comprehensible, as the seminar continued, it became less and less logical for me. A lot of concepts were new for me and were touched on only briefly, hence I lost parts of the seminar. Just like Dijkgraaf said one could easily get lost in H space while I didn’t even know what is comprised. Despite me not following all the content, it still widened my horizon, as it became apparent how much there is around I still don’t know anything about. A lot of those concepts and theories are also more or less related to my field of study and are therefore worth taking a closer look at some time. Although slightly off topic, when Cees Dekker introduced Dijkgraaf, he told us about some of the many committees, boards or councils Dijkgraaf has working in. I found this interesting as well, besides his own research he is also looking at science from different levels and angles, which I believe is anything but boring.

All in all life is at the center of the sizescales. Beyond the cellular and organelle level there is yet so much to be discovered. In the future a beautiful goal
would be to implement concepts in the universe scale into the atomic scale and vice versa. Personally I am most interested in some of the quantum related theories and concepts.

What you can learn from computer modelling

Speaker: Christine Jacobs-Wagner
Department: Casimir Research School
Subject: How to achieve cellular replication without fail: lessons from bacterial cells
Location: Delft
Date: October 13, 2017

Although Christine Jacobs-Wagner studied biochemistry in college, she would describe herself more as a cell biologist. According to her, one is not defined by education, but rather by the questions they pose themselves. That’s why her lab is very multidisciplinary, which made her seminar really interesting. I liked the way she didn’t just come to Delft to lecture us about what’s she’s done, but rather to get feedback from the scientists here, who might have a stronger modelling background than hers. This is how science should work, and it’s a great feeling to be a part of it.

She spoke about the importance of distributing plasmids evenly during cell division. If one of the daughter cells doesn’t inherit an essential plasmid for some reason, it will not survive. That’s why it is crucial to have a method in place to guarantee the survival of both daughter cells. The ParA and ParB proteins make up such a system. This was the focus of her research.

Plasmids should be distributed like these green dots

The ParA proteins bind to the nucleoid of a bacterium, and the ParB associates with plasmid DNA. When they interact, ParB induces a reaction which breaks the ParA-DNA bond. This is all well understood, but how would this have the desired effect of distributing all plasmids evenly? Well, it might be easier to observe what happens when there’s only one plasmid in the cell. It starts to oscillate along the long axis, but why?



Then she proceeded with an in silico model, a computer simulation. Unfortunately, the first model didn’t show the desired behaviour. The plasmid made a random walk, so the Par proteins didn’t do anything. At least, not until she adapted the model to make the DNA non-static. She could model ParA molecules as tiny springs, which oscillate around an equilibrium position. This was a very small change, but it had a great impact. It was all she needed to accurately model the oscillatory behaviour.

It was really cool to see such a small change make such a big difference. For further research and exploration of the ParA-B system, an analytical model would be useful, but that will also be a big challenge. I’m excited for the future!