Real-time observation of translation of single mRNA molecules in live cells.

Speaker: Marvin Tanenbaum
Department: Department of Bionanoscience
Subject: Real-time observation of translation of single mRNA molecules in live cells.
Location: Delft University of Technology

Date: 24 March 2017
Author: Romano van Genderen

The research by professor Tanenbaum was about the kinetics of translation. He started by talking about how many genes, about 20%, oscillate in gene expression during the cell cycle, setting off processes of division and differentiation. For this to happen, a very strong regulation of the genes is necessary. This happens on many levels, not only on the scale of transcription, but also translation. Translational regulation has been shown to be the most important process to regulate how much of a certain protein is produced. This regulation happens through miRNA and RNA binding proteins.

In order to more carefully study this regulation, it is needed to see the RNA translation in action. A relatively old method for visualizing RNA was developed by Singer labs. They build in a series of hairpins in the RNA. These hairpins are a binding site for a protein called MCP. This MCP protein has a GFP tag to allow for visualization.

Showing the translation product sounds like something that would not be too hard. Just let the ribosome translate the RNA for GFP and it should be visible. But a problem about this method is that you create a lot of background noise from the free-floating GFP. Another problem is that GFP needs some time to maturate, which takes longer than the translation. So they used a free-floating GFP-antibody complex that binds the protein that is being synthesized. This SunTag system they developed is very bright and allows for very good visualization.


Fig 1. An overview of the SunTag system. You can see them being used to look at proteins that are being synthesized (Tanenbaum et al, A Protein-Tagging System for Signal Amplification for Signal Amplification in Gene Expression and Fluorescence Imaging, Cell 159)

So now you can combine the two aforementioned approaches. First fuse some small peptides to your protein of interest. Then let green antibodies bind the peptides. At the same time, you attach mCherry to a newer form of MCP, PP7 and let it bind the RNA hairpins which are non-coding. Wherever you see yellow, active translation is going on. When PP7 is injected into the cytoplasm, it can now be used to follow a piece of mRNA from the export into the cytoplasm until its eventual degradation.

Using this technique a few experiments were done.

Firstly, they were able to count the number of ribosomes on a single piece of mRNA, showing that the average number was around 20.

Next, they showed the translation speed. Because when the translation would be very slow, the ribosome signal would slowly dim after adding a translation initiation inhibiting drug. If translation would be very fast, the signal would be lost immediately.

Other research was done on the regulation of translation. They did find that specific RNA cutting proteins only work when RNApol collides with them, “bumping them off”. The cutting step of this protein works automatically, but they need a collision with RNApol to release the protein and therefore the cut strand.

I did really enjoy the technical overview of the versatile SunTag procedure and the applications of it. I do expect even more findings to come from this method, especially if this method can also be expanded to work on DNA as well. This would be a good improvement of the method. But I continue to doubt if understanding of the kinetics of translation has any practical applications.

Light Sheet Microscopy

  • Speaker:             Malte Wachsmuth
  • Department:     Cell biology 
  • Location:            Erasmus MC
  • Date:                    23-02-2017
  • Author:               Katja Slangewal

Light-sheet microscopy is a microscopy technique optimized by a start-up company called Luxendo (part of EMBL). This technique is special because it enables live cell imaging for an increased amount of time with a resolution close to confocal resolution. The main idea behind light-sheet microscopy is the uncoupling of the illumination and detection light paths. The illuminating beam illuminates a thin sheet of the sample (2-8μm), which is in the focal plane of the detection lens. This enables full area detection with a single light sheet (figure 1, right). This creates an advantage over confocal microscopes, since they use point-wise raster scanning. This leads to the illumination of a quite large part of the sample over time (figure 1, left). So, light-sheet microscopy reduces the amount of light needed to image your sample. This reduces the photobleaching of your samples. Also, by imaging with a single light-sheet is becomes possible to capture your sample in one single shot. This makes light-sheet imaging ideal for the imaging of dynamic processes in live specimen. One disadvantage or possible problem could be the intensity drop of the illuminating beam. The amount of intensity drop is dependent on your sample and labeling, so it might not be a problem in most cases. However, there is a way to reduce the intensity drop. By using dual illumination (simultaneously from the front and back of the sample), the intensity drop can be reduced.

seminar 7 im1

Figure 1: Light-sheet microscopy (right) versus confocal microscopy (left). Light-sheet microscopy drastically reduces the amount of illumination of your sample, thereby decreasing photobleaching. Source:

The MuVi-SPIM (Multiview selective-plane illumination microscope) is one of the microscopes using light-sheet microscopy. The MuVi-SPIM is based on four objective lenses. Two lenses are used for illumination of the sample and two lenses are used for the detection of the fluorescent signal. The four lenses give four different views on your sample, which can be fused to one optimized image (figure 2). This way you can image larger living specimen without rotating them, thereby reducing the acquisition time.

seminar 7 im2

Figure 2: The MuVi-SPIM: by using four objective lenses and adding the four separate images an optimal image can be formed, thereby reducing noise and increasing the signal. Source:

Besides the MuVi-SPIM there are more possible geometries which are able to use the principles of light-sheet microscopy. One example is the InVi-SPIM (inverted view selective-plane illumination microscope). This geometry uses only two objective lenses, one for illumination and one for detection (figure 3). The InVi-SPIM has been developed for long-term 3D imaging of living specimen. It has an inverted microscope configuration, which makes it easier to access the sample chamber. According to Wachsmuth, your specimen will be able to stay alive for approximately 2 days in the chamber. The InVi-SPIM is for instance very useful for stem cell differentiation assays. This because of the lower amount of photobleaching compared to a confocal microscope, but with similar resolution. A small disadvantage is the inability to use dual illumination (illuminating your sample from the front and back simultaneously).

seminar 7 im3

Figure 3: The InVi-SPIM enables the imaging of living specimen for longer periods of time. Source:

Light-sheet microscopy makes it possible to image two different parts of a sample at the same time. One could for instance image both the heart of a zebrafish and its blood flow in the tail. This is not possible with a confocal microscope, since the confocal microscope needs time to image by point-wise raster scanning. This together with the lower amount of photobleaching and higher imaging speed makes light-sheet microscopy a promising microscopy technique.

This seminar was different from the other seminars I have visited so far. This was mainly because Malte Wachsmuth was representing a company instead of a research group. This gave the talk a bit the appearance of a sales pitch. However, it was still very interesting. I hadn’t heard about light sheet microscopy before and I think it sounds like an interesting technique. Malte was a very enthusiastic speaker and he had a very clear talk.


Information processing in the neural and gene regulatory networks

Aïsha Mientjes


Seminar 4:

Speaker:  Gasper Tkacik             

Department: Bionanoscience

Subject: Information processing in the neural and gene regulatory networks

Location: TU Delft          

Date: 22-03       

Dr. Tkacik dived up his lecture in several parts. The first part dealt with history. He explained a little bit about Shannon’s information theory. Shannon stated that in communication there are three parts: the source, the channel and the receiver. Dr. Tkacik then explained  a little bit about the mutual information theory: the measure for the ability to send and recover signals through a noisy channel. Shannon’s theory provides a framework for understanding biological processing.

Part two dealt with the retina as a coding device: going beyond single neurons to neural populations. Dr. Tkacik showed us a movie of fish in which he could show the response of neurons. The brain receives a binary signal, but there are still many questions relating to these signals. Dr. Tkacik concerns himself with whether the pattern can be converted back into the initial movie. He can actually do this, and there is a pretty good correspondence.

Part 3 of the lecture was about positional information. In many cellular processes, cellular specification is q=guided by positional information. In this lecture, some questions were asked about this:

  • How much is needed?
  • Are some patterns better than others?
  • How much information do patterns give?
  • How do you read the positional code?seminar 4This image shows the French flag model, an important model in positional information.

Information theory can be used to quantify many biological processes, such as positional information.

The final part of the lecture dealt with perspectives for the future.

  1. New data allows us to observe networks in action.
  2. Quantitative measurements can be done for networks.
  3. Quantifying can help with efficient coding.
  4. Computation will play a big role.
  5. Evolutionary dynamics can be studied.

This concluded the lecture.

This was the second seminar I attended at the TU Delft. I found this topic slightly easier to follow than the last TU Delft seminar. This was mainly because I has some knowledge on this topic from evolutionary developmental biology. I found it very interesting to see that many biological processes can be quantified, which will make studying them a lot easier. I found this seminar very interesting and the lecturer was very passionate and could tell us a lot.

All in all, I found it a very interesting and educational seminar.

Quantum optomechanics – exploring mechanical motion in the quantum regime

Aïsha Mientjes


Seminar 3:

Speaker:  Markus Aspelmeyer  

Department: Nanoscience/Physics

Subject: Quantum Optomechanics – exploring mechanical motion in the quantum regime.

Location: TU Delft          

Date: 02-03       

Dr. Aspelmeyer started out the lecture by explaining what quantum optomechanics is. It is the combination of opto mechanics and quantum optics. In quantum optics, fluctuations infer with the measurements. This is referred to as the standard quantum limit. Quantum optomechanics is the full quantum toolbox to prepare and control mechanical quantum states via photonic quantum states.

He went on to state several quantum states.

  1. Quantum ground state of motion
  2. Quantum states of motion
  3. Non-Gaussian quantum states of motion
  4. Quantum entanglement

The next part of the lecture dealt with applications of quantum optomechanics, some examples are:

  • On chip quantum information processing
  • Quantum hybrid devices
  • New coating techniques

 seminar 3



This image shows a quantum nanodevice, one of the applications of quantum optomechanics.


The precision of many quantum measurements is limited by the coating that is used. Coatings which do not function well are the most important problem in our measurements of space and time. We have to deal with things such as Brownian motion and thermal fluctuations.

The team of Dr. Aspelmeyer mainly concerns themselves with 2 questions:

  1. How small can a source mass be?
  2. How massive can a quantum system be?

This concluded his lecture.

This was the first seminar I attended at the TU Delft. The previous two had both been at the Erasmus MC ant therefore this one had a very different character. It dealt much more with the applications of physics and mathematics and was not focussed on human health. Despite this seminar being different from the past two I attended, I enjoyed this very much. The topic is quite abstract and difficult to grasp, but Dr. Aspelmeyer explained everything very well. He was very enthusiastic about the work being done in this field currently, which made the seminar very enjoyable to listen to.

I found it very interesting to learn how something as simple as a coating can have such major effects on the measurements being done. It amazed me how something so simple can be so limiting. All in all, I found it a very interesting and enjoyable seminar.

Evolution and Assembly of Eukaryotic Chromatin

Speaker: Fransesca Mattiroli

Department: Lugi Lab, University of Colorado Boulder

Subject: Evolution and assembly of eukaryotic Chromatin

Location: TU Delft, Bionanoscience department

Date: 10-02-2017

Author: Mirte Golverdingen


Fransesca Mattiroli’s research is focussed on the DNA packaging units called nucleosomes. These structures organize DNA in the eukaryotic cell nucleus. Nucleosomes are formed by an octameric complex of folded histone dimers called the H3-H4 and H2A-H2B dimers. In mammals, the histones have histone tails which highly contribute to post-translational modifications and they stabilize the nucleosome. Nucleosomes need to assemble and disassemble when they bind to the genome DNA. Histone modifications and variants are dynamic and can promote or inhibit certain interactions. The nucleosome dynamics and compositions have a direct effect on transcription, translation and repair.

The first main interest of Mattiroli is the evolutionary origin of the nucleosome. The nucleosomes are very well conserved through species. Mattiroli focusses on the structural conservation of the histone dimers in Archaea. They, however, miss the tails that contribute to post-translational modification. So, how do these species organize their archaeal genome?

The archaeal histone binding to DNA is similar to eukaryotic histone binding. Archael histones, however, do not form octamers. They can form a much longer structure instead, called nucleosomal ramps. In Vivo, this structure also forms, the longest ramp they found was 90 bp long. So, they found a new way of arranging histone DNA complexes.

Histones are formed on the DNA in two steps, first, two H3-H4 dimers form a tetrasome, then two H2A-H2B dimers attach to this tetrasome forming a nucleosome. Histone chaperones shield the charges of the histones and facilitate their deposition on DNA. However, not much is known on how the chaperones actually contribute to this deposition step. The Chromatin Assembly Factor 1, CAF-1, is Mattiroli’s main interest. CAF-1 mediates in this histone deposition step and is essential in multicellular organisms. Matteroli tried to understand how CAF-1 contributes to the deposition step.

Mattiroli’s first step was to research how CAF-1 binds the H3-H4 dimer. She used mass spectrometry (HX-MS) with a hydrogen-deuterium exchange. She could, in this way, measure the change in mass and which regions have the largest changes in deuterium uptake. This region could then be the binding site of CAF-1 on H3-H4. When CAF-1 binds to the dimer, they see a stabilization of the dimer. This result indicates the following hypothesis: Only if a H3-H4 dimer is bound to CAF-1 it can form a tetrasome.

A next step for Mattiroli was to test if CAF-1 can form nucleosomes in vitro, in absence of other proteins. To test this, Mattiroli mixed CAF-1, histones and DNA, treat them with micrcococcal nuclease to digest unprotected DNA and purified and quantified the length of DNA covered by histones. The result showed that CAF-1 is able to assemble tetrasomes, and therefore enabling nucleosome formation in vitro.

So, how is the H3-H4 tetrasome on the DNA formed? Mattiroli used increased lengths of DNA, to trap any intermediates in the process. Mattiroli showed that the forming of the H3-H4 dimer activates the DNA binding of the dimer. The key intermediate that mediates the DNA binding results to be two CAF-1 units. This was the most interesting result so far, because it was never showed before that two independent CAF-1 were involved in the H3-H4 DNA binding.

The interesting and clear seminar showed again how complex the system of DNA and all the DNA-interacting molecules is. The research of Mattiroli gives a good foundation for more research to nucleosomes and their interaction with DNA. Bringing us closer to fully understand the biological system of DNA.

Honours 7

Figure 1. Canonical and variant nucleosomes

(A) Elements of the histone fold and structures of Xenopus leavis H2A–H2B, H3–H4 and (H3–H4)2 (PDB ID: 1KX5). (B) Structure of the canonical Xenopus leavis nucleosome (PDB ID: 1KX5). Other nucleosome structures, such as the human nucleosome, are structurally similar. (C) Structure of the CenH3CENP‐A‐containing nucleosome (PDB ID: 3AN2). (D) Zoomed view of the αN helix of CenH3CENP‐A (left) and H3 (right) involved in stabilizing the DNA ends. Histone H3 is blue, CenH3CENP‐A is cyan, H4 is green, H2A is yellow, H2B is red, and DNA is white.

Adapted From: Mattiroli, F., D’Arcy, S., & Luger, K. (2015). The right place at the right time: chaperoning core histone variants. EMBO reports, e201540840.

Crosstalk of Immune and Nervous Systems

Speaker: Frauke Zipp
Department: Neurology, Mainz (Germany)
Location: Erasmus MC Rotterdam
Date: February 6, 2017
Author: Teun Huijben

Frauke Zipp is the head of the neuro-immunology research group in the Department of Neurology of the Medical University of Mainz, Germany. The main focus of her research is gaining better understanding of the complex interplay between the immune system and the central nervous system.

Many diseases are caused by problems in the interactions between the immune system and the central nervous system (CNS), examples are: Multiple Sclerosis (MS), Acute Disseminated Encephalomyelitis (ADEM), Meningitis, strokes, migraine and Alzheimers, Parkinsons and Huntington disease. Of all these diseases, MS is the best model disease of this interaction, since it is a chronic inflammation of the central nervous system.

The hypothesis of the cause of MS is an auto-immune respons where T-cells attack the central nervous system during the young adolescence. These CNS-specific T-cells are activated in some way and cross the blood-brain barrier. Arrived in the brain they are re-stimulated by seeing the CNS-antigens and their activation induces a cascade of reactions ultimately resulting in demyelination of axons (figure 1). Myelin is a fatty substance wrapped around axons to increase their electrical conductivity and provides mechanical protection. When this myelin is removed, the axons get damaged and the resulting neural injury will have all sort of effects.

demyelinationFigure 1: Demyelination of axons in multiple sclerosis. As an effect of the auto-immune attack of T-cells in the brain, the myelin around axons is removed and axon function disrupted. [1]

How the demyelination is caused by the immune respons is not exactly known. One idea is that the activated lymphocytes enter the CNS and attack oligodendrocytes, cells that produce and maintain the myelin. Another idea is that cytotoxic (Cd8+) and T-helper (Cd4 + and Th17) cells directly attack the axons.

Remarkable is that 40 percent of the patients does not have extreme pathology effect and show a pattern of relapses and remissions. This suggest some repair of the CNS during these remissions. Frauke Zipp and her group are interested in this repair and also in better understanding MS in general to come up with new therapies.

To study MS they use an EAE (Experimental Autoimmune Encephalitis) mouse model that mimics the human disease. Using cultures of these cells it is possible to follow the immune respons of the brain by imaging living cells. This in vivo research led to multiple new concepts.

The first one is counterbalancing the inflammatory response. Microglia cells are the immune cells of the brain that can be best compared with macrophages. They found that microglia cells are able to catch Th17 cells using their long processes and engulf them by phagocytosis. Hereby defending the CNS against the mistaken attack of the immune system. Another concept is the discovery that T-helper-2 cells (Th2) are able to repair the nervous system during periods of remission. They do this by inducing regeneration of axons damaged by the immune system.

Overal, it was a quite difficult seminar to follow given our limited knowledge about the brain and the many medical terms used by Fauke Zipp. However, it is interesting and promising that her research has led to completely new concepts regarding the understanding of multiple sclerosis. And hopefully more research will result in newer and better therapies to defeat this disease.


Further investigation to the role of Arf1 in the Golgi apparatus

Speaker: Francesca Bottanelli
Yale University
Subject: Live-cell nanoscopy of protein sorting at the Golgi
Location: A1.100 (TU Delft)
Date: 14-11-2016

Kristian Blom

At the 14th of November I visited a BN seminar given by dr. Francesca Bottanelli, a postdoctoral associate in cell biology in the Rothman Lab at Yale University. Dr. Bottanelli is a cell biologist who is interested in the use of Stimulated Emission Depletion (STED) for living cell imaging. At the moment she uses STED to image COPI protein dynamics at the Golgi apparatus in mammalian cells. 

Dr. Bottanelli started the talk by introducing the main actor of her research: the Golgi apparatus. This organelle is the main sorting station of the cell and despite decades of research we are still far from fully understanding how it functions. Proteins that are synthesized in the endoplasmic reticulum are packaged into vesicles, which then fuse with the Golgi apparatus. Thereafter they are transported to the right location in the cell. While the machinery and molecular interactions involved in cargo sorting have been extensively investigated in vitro, there is a lack of understanding of the dynamics and nanoscale organization in living cells, since intracellular transport occurs over extremely short distances of a few 100 nm. A little progress is made over the past decade due to the difficulty to image molecular processes in the intrinsically crowded perinuclear area using standard diffraction limited imaging techniques.

After the introduction we went further into detail about STED. This imaging technique is part of the so called super-resolution microscope techniques, which means that the resolution that you can get with this technique bypasses the diffraction limit. In conventional fluorescence microscopy the electrons of a fluorophore are excited by incoming light of a certain wavelength, and thereafter by relaxation of the excited electron light of one specific wavelength is emitted back by the fluorophore (green arrow figure 1). However, with STED it is possible to force the excited electron into a higher relaxed vibration state than the fluorescence transition would enter, causing the released photon to be red-shifted (orange arrow figure 1). To make this alternative emission occur, an incident photon must strike the fluorophore. One can achieve super resolution by depleting fluorescence in specific regions of the sample while leaving a center focal spot active to emit fluorescence.

Figure 1 – A Jablonski diagram for the process of fluorescence and STED. Blue: Excitation of an fluorophore’s electron to a higher energy state. Green: Fluorescence – Relaxation of the excited electron. Due to the drop in energy light is emitted. Orange: STED – Relaxation of the excited electron to a higher energy state compared to the orange version. Due to the smaller energy drop during relaxation, light with a longer wavelength is emitted.

Dr. Bottanelli developed a novel labeling strategy for dual-color live-cell STED. Taking advantage of gene editing techniques (CRISPR/Cas9) and her novel live-cell STED labeling strategy she took a careful look at the role of ARF1, a protein localized in the Golgi apparatus that has a central role in the formation of COPI vesicles at the Golgi. The role of ARF is mainly to recruit adaptors and coat proteins for the formation of transport carriers. However, Dr. Botanelli found out that besides its role in generating COPI vesicles by recruiting Coatomer at the the Golgi, ARF1 also is involved in the formation of anterograde (from ER to Golgi) and retrograde (from Golgi to ER) tubular carriers.

Due to my lack of knowledge about the Golgi apparatus and the different proteins that are involved in the transportation process, it was rather hard for me to follow the talk. However, once I started to put everything on paper, more and more about what was told became clear for me. Afterwards I asked myself the question whether dr. Botanelli already found out if these anterograde and retrograde carriers are the main transportation systems that allow for the protein dynamics between the ER and Golgi apparatus. Since I did not followed everything during the talk, it could be that I missed that part. If that is not the case it might be a nice topic to do research about for in the future.

Spacer acquisition and regulation of CRISPR-Cas systems


Speaker: Peter Fineran

Subject: Spacer acquisition and regulation of CRISPR-Cas systems

Location: Delft

Department: Bionanoscience

Date: 21-02-2017

Author: Carolien Bastiaanssen

The Fineran lab is interested in the interactions between mobile genetic elements and bacteria. They study the defense mechanisms that bacteria evolved to protect themselves against invaders such as bacteriophages. Their research focusses on one particular type of defense mechanisms, the CRISPR-Cas adaptive immune systems. In his talk Peter Fineran first gave a short recap of the CRISPR-Cas systems. Next he explained how the CRISPR-Cas systems form their immunological memory and he presented recent work on the regulating role of quorum sensing communication in the CRISPR-Cas systems.

In short the CRISPR-Cas systems work in three stages. The first stage is the acquisition stage where the bacteria forms immunological memory by incorporating part of the foreign DNA into its own genome at the CRISPR locus. Once incorporated, this sequence is referred to as a spacer. The second stage is the expression and processing stage. This involves the transcription of the CRISPR locus leading to the production of CRISPR RNAs (crRNAs). Each crRNA contains a spacer. In the third stage, the interference stage, the crRNAs with the help of their spacer recognize invading DNA as foreign and the invader is degraded. The many different types of CRISPR-Cas systems all work following the adaptation, expression and interference stages.

CRISPR three stages

Figure 1: Stages of the CRISPR-Cas immune systems. In stage 1 foreign DNA is acquired and incorporated as spacers. In stage 2 the CRISPR locus is transcribed and the RNA is processed to form mature CRISPR RNAs (crRNAs). In stage 3 the crRNAs target viral elements with the spacer as a guide. Source:

The questions that intrigued the Fineran lab included how adaptation occurs and what part of the plasmid is taken up by the bacteria. To answer these questions they added plasmids to a population of bacteria and subsequently analyzed the bacterial genomes. Surprisingly there was a lot of acquisition of spacers from the bacteria’s own chromosome. This phenomenon is like an autoimmune defect and it occurs constantly in wild-type cells. However, chromosomal spacers are counter-selected as they typically result in cell death. Fineran and his colleagues found that 93% of the times the last acquired spacer in the CRISPR array before cell death was from the bacterial chromosome. If CRISPR-Cas is so costly, why do bacteria still have this immune system? Does this mean that defense is increased with increased vulnerability? And how do bacteria regulate CRISPR-Cas immunity?

It is known that high cell densities of bacteria are prone to horizontal gene transfer because phages can spread rapidly through a dense population. One way in which bacteria can determine the cell density and regulate gene expression accordingly is through a form of communication called quorum sensing (QS). In low cell density there is are low amounts of the signaling molecules and in high cell density the signaling molecules accumulate, causing an upregulation of certain genes. Fineran and his colleagues set out to study the possible role of QS in regulating CRISPR-Cas immunity. They showed that mutant strains that were unable of QS were more vulnerable for invading plasmids because they had reduced CRISPR-Cas activity. At low cell density there is a repressor, SmaR, that shuts down CRISPR-Cas activity. At high cell density the signaling molecule AHL represses SmaR and CRISPR-Cas activity is no longer repressed. Hence, at high cell density there is increased CRISPR immunity and at low cell density CRSIPR immunity is reduced, leading to less autoimmune effects and thus lower fitness costs.


Figure 2: CRISPR-Cas immunity is regulated through quorum sensing. When the cell density is low the concentration of AHL is also low and SmaR represses CRISPR expression. When the cell density is high the concentration of AHL is high and AHL represses SmaR. As there is no SmaR to repress CRISPR expression, CRISPR expression is upregulated. Thus at high cell densities the cells are in a higher state of defense than at low cell densities, thereby reducing the costs of the CRISPR-Cas system when there is no high threat. Source: Patterson, A. G. et al. Quorum Sensing Controls Adaptive Immunity through the Regulation of Multiple CRISPR-Cas Systems. Mol. Cell 64, 1102–1108 (2017).

CRISPR is a hot topic and it the CRISPR-Cas9 system is commonly used as a gene editing technique. Therefore, I find it quite surprising how many aspects of the CRISPR systems are still to be unraveled. The research performed by the Fineran lab provides insights in how bacteria control the rather large fitness costs of the CRSIPR systems. All in all, the talk was clear and a pleasure to attend due to the enthusiasm of the speaker.

Deciphering the functional organization of neuronal circuits controlling locomotion

Speaker: Ole Kiehn
Department: Neuroscience department
Subject: Deciphering the functional organization of neuronal circuits controlling locomotion
Location: Erasmus MC
Date: 06-03-2017
Author: Renée van der Winden

Ole Kiehn came to talk to us about his research on how locomotion is controlled by the nervous system. All the research he did was on mice, so everything that I will explain below has been seen in mice and not necessarily in humans. Dr. Kiehn distinguished two key features in locomotion, namely pattern generation and rhythm generation. The pattern generation is controlled by a dual system consisting of V0 neurons and non-V0 neurons in the spinal cord. The V0 neurons are split up into inhibitory and excitatory neurons. Which type they are is determined by the different transcription factors that are expressed along the spinal cord. By working together these neurons determine whether or not the mice move their left and right limbs synchronously or alternatingly. It turned out this decision is also influenced by the speed with which the mice move.

Seminar 4Figure 1: Schematic overview of pattern generation in mice

The rhythm generation happens in the brainstem instead of the spinal cord. Now the V2a neurons play an important role. They are excitatory and turned out to be essential for left/right alternation of the limbs. Another important factor here is the transcription factor Shox2. This is expressed in the ventral part of the spinal cord and works together with the transcription factor Chx10. It turned out that when the expression of Shox2 was affected, this reduced the frequency of the limb movement in locomotion. Clearly, Shox2 is involved with rhythm. It is thought it is driven by V2a neurons.

Dr. Kiehn also discussed how stopping and starting is regulated. This, too, happens in the brainstem. The mechanism used results in an active stop (as opposed to simply ‘not starting’ anymore). Again the V2a neurons play a role. They express Chx10 and act on an inhibitory network in the spinal cord to result in a controlled stopping of the locomotion. For starting movement the mesencephalic locomotor region (MLR) is the key player. This consists of two parts: the CNF and PPN. By stimulating the different regions it was found out that CNF invokes motion of all speeds and PPN only invokes motion of low speeds. Therefore it is thought that CNF is involved with escaping and PPN with explorative movement.

I thought this seminar was very interesting. I am interested in how the brain works and how it leads to people performing certain actions and having certain thoughts. I would like to explore the possibility of eventually doing research in the neuroscience field. I also thought the seminar was relatively easy to understand, which made it more enjoyable to listen to.

Quantum Optomechanics

Speaker: Markus Aspelmeyer
Department: Kavli Colloqium
Subject: Quantum Optomechanics – exploring mechanical motion in the quantum regime
Location: TU Delft
Date: 01-03-2017
Author: Renée van der Winden

Markus Aspelmeyer came to talk to us about his research in establishing mechanical motion in the quantum regime. Techniques for this already exist, but only for single ions. Dr. Aspelmeyer wants to upscale this to up to 10^13 atoms. He first explained to us the basic and fundamental principle of his research. The setup for his experiments consists of a moveable mirror which is attached to a stationary wall with a spring. On the other side of the mirror, opposite the wall, is a lens through which light falls on the mirror. The photons that hit the mirror in this way, can cause it to be pushed back. This in turn changes the phase of the light in a nonlinear way. In this set-up the mirror functions as a harmonic oscillator. This leads to a position-dependent force and, because this is a retarded force, also a momentum-dependent force. This gives you control over the force and the movement of the mirror. However, photons leak to the environment and they leave the cavity between the lens and the mirror. This leads to decoherence and gives the need for a more isolated system.


Figure 1: Very basic representation of the set-up used

The talk continued with a couple of applications. The technique can, amongst others, be used for mechanical memory and electromagnetically induced transparency. A surprise application that Dr. Aspelmeyer discovered in his lab was to improve the mechanical coating that is used in optomechanical systems. Right now these coatings are quite bad, which leads to a lot of dissipation to the environment. In fact, this is currently the limiting factor for systems such as optical clocks and gravitational wave detectors. Improving this coating will thus have a major influence on the operating of these systems.

I feel like I have not fully grasped the essence of the research that Dr. Aspelmeyer has done, because I did not really understand what it improved in relation to the current state of events. Nevertheless, I did enjoy the talk, not in the least because of Dr. Aspelmeyer’s enthusiasm about the subject. I do not intend on pursuing a career in physics, but the talk was still interesting.