Category: Articles

Tumor suppressor genes code for proteins which protect cells from one step on the path to cancer. These proteins can sense DNA damage and prevent cell division in order not to pass on the damage to the daughter cells. Tumor suppressors have damping effects on the cell cycle and can promote cell death (apoptosis). One of the most important tumor suppressors is called p53, also known as “the guardian of the genome”. P53 has been nominated as the molecule of the year in 1993 by the journal Science. However, I felt it’s time to acknowledge these guardians with a little poem:

Dear tumor suppressor gene,

I guess we can’t thank you enough
for protecting us when times get rough
for keeping growth under control
when cell cycle goes rock ‘n’ roll

If our genome has a nick
you immediately put a stick
between the wheels of proliferation
so cell cycle can’t reach its final destination

Your nemesis named oncogene
is always waiting behind the scene
to make cell cycle go wild and crazy
but you are prepared and never lazy

After swords have been crossed
and the fight is over and lost
You bring some decent roses
to the cell’s funeral: the apoptosis.

It sems that palm reading will sooner or later be replaced by poop-reading. The human psyche is complex and accumulating evidence shows that it is not only ‘us’ beeing responsible for our moods, feelings, and personality. Our brain is massively influenced by the composition of our subtenants: the bacteria. A human carries ten times more bacteria than own cells, an entity called the „microbiome“.

Bacteria suffer from bad reputation but most of them are harmless and some are useful and necessary for our survival. Bacteria regulate our metabolism and educate our immune system. We get the first dose of bacteria from our mum’s birth canal and by breastfeeding and our bacterial fingerprint will always resemble that of our mum.

Gut bacteria are using a can phone, the so called vagus nerve, to signal between the gut and the brain. The spoken language is a cocktail of neurotransmitters, which are synthesized and understood by brain cells and bacteria. Studies have found that the microbiome of depressed people has a different composition than that of happy people (1). Instead of Prozac and Valium, yoghurt enriched with good bacteria could be the treatment of these conditions in the future (2).

Our bacterial companions can also manipulate our behaviour for their own needs. The feeling of happiness is induced by a specific neurotransmitter which can be synthesized by gut bacteria. Happy people are more social and more motivated to go out and meet other people which in turn gives our bacteria the chance to spread and exchange with other bacteria (3).

But our microbiome also seems to influence our partner choice: A study found that we choose our partners according to the similarity of our (mouth) microbiome (4). This decision makes sense from an evolutionary perpective: the more similar microbiomes are, the lower the challenge for the immunesystem and the threat for our health. An approach that could revolutionize dating platforms like Tinder and co…

Considering the above metioned, it is not absurd that scientists experiment with poop transplants (Fecal Microbiota Transplantation, FMT) in order to treat gut but also mental diseases. Stool from healthy donors is introduced into the guts of patients with the hope that the good bacteria will settle down and re-colonize the gut (5).

I hope, I could give you a new insight into the „gut feeling“. And always remember: Bacteria is the only culture some people have…

XOXO, Your Nerd

 

1. Latalova et al., Can gut microbes play a role in mental disorders and their treatment? Psychiatr Danub. 2017 Mar;29(1):28-30.
2. Steenbergen et al., A randomized controlled trial to test the effect of multispecies probiotics on cognitive reactivity to sad mood. Brain Behav Immun. 2015 Aug;48:258-64.
3. Montiel-Castro et al., Social neuroeconomics: the influence of microbiota in partner-choice and sociality. Curr Pharm Des. 2014;20(29):4774-83.
4. Kort et al., Shaping the oral microbiota through intimate kissing. 2014 Nov 17;2:41.
5. Vindigni et al., Fecal Microbiota Transplantation. Gastroenterol Clin North Am. 2017 Mar;46(1):171-185.

Mitochondria are bacteria ancestors engulfed by cells millions of years ago. By mutual consent they became permanent subtenants as described by the endosymbiontic hypothesis. Their major job in the cell is to produce energy by the use of oxygen. Therefore, mitochondria are often refered to as „powerhouses“ of the cell. Mitochondria control the metabolic flow within cells by linking the degradation of sugars, fats, and amino acids to the generation of energy by oxygen.

But mitochondria are more than just energy deliverers. They are mediators of cell death and control cellular calcium balance. Further, mitochondria are involved in the process of aging; it was shown that specific mitochondrial disturbances can increase lifespan in worms by the upregulation of genes which control the stability of proteins (1).

Mitochondria are promising targets in medicine. They are the cell’s Achilles heel in stroke and myocardial infarction. Blockage of a blood vessel induces energy depletion with devastating consequences for high performance cells like neurons and cardiomyocytes. But also pathologies like Alzheimer’s disease and Parkinson’ disease seem to have a mitochondrial component: defective mitochondrial fission and fusion.  Bypassing mitochondrial activity in order to become independent of oxygen , known as the „Warburg effect“, is a hallmark of agressive cancer cells (2).

As a leftover of their bacterial past, mitochondria have heir own circular DNA which codes for 37 genes. During evolution, they outsourced parts of their genome to the nuclear DNA. So whenever the mitochondria need to activate these genes, they must tell the nucleus.

Epigenetic modifications of the DNA control the activity of genes. Environmental stimuli, like food availabilty, are translated into the genome by epigenetic mechanisms. As part of the metabolic system,  mitochondria are sensors of environmental changes and can forward these to the genome by an altered metabolic output. This output contains the building blocks for epigenetic modifications, like DNA methylation and histone marks. In consequence, starving conditions or overfeeding influence epigenetic modifications and subsequently the activity of genes (3).

Mitochondrial DNA itself was found to be methylated and organized with proteins, but not histones, into a structure called nucleoid. The existence of a mitochondrial epigenome and the talk back between mitochondria and the epigenome of the nuclear DNA adds a new level of complexity to the model of genomic regulation. Mitochondria seem to be the interface of the metabolic-epigenome-genome axis. They are capable of nuclear reprogramming thereby establishing a  nutritional memory. Be aware of that during your next chocolate orgy 😉

XOXO,Your Nerd

1. Tian et al. Mitochondrial Stress Induces Chromatin Reorganization to Promote Longevity and UPR(mt). Cell. 2016 May 19;165(5):1197-208
2. Margineantu et al. Mitochondrial functions in stem cells. Curr Opin Genet Dev. 2016 Jun;38:110-117)
3. Kirmes et al. A transient ischemic environment induces reversible compaction of chromatin Genome Biol. 2015 Nov 5;16:246.

 

The unknown of the outer space fascinates humankind since ever: the universe, it’s galaxies, stars, dark matter, black holes and extraterrestrial life. Every galaxy consists of a particular arrangement of stars, dust, gas, and (potentionally) dark matter. A galaxy has a certain position within the universe but galaxies are not static; they can move within billions of lightyears and interact with other galaxies. The detailed analysis of the universe from the earth is limited by resolution, which is impaired by the earth‘s atmosphere, the gigantic distance to the objects of interest and their amount of light emission. Since 1990, the Hubble Space Telescope sends images from outer space with constantly improved resolution.

But there is another universe, also hardly explored, but tiny and as close as it could be since it is located in ourselves, inside the cell nucleus. This universe consists of chromosome-galaxies, gene-stars and the dark matter of junk DNA. Like the Hubble Telescope, scientists developed super-resolution microscopy techniques to overcome the limitations of resolution and now we begin to understand which dynamic and functional wonderland exists inside us: the nucleus-universe.

It was thought that the interphase nucleus, where chromosomes are decondensed and gene trancription takes place, resembles a plate of spaghetti. But actually, chromosomes occupy distinct territories inside the nucleus and form genomic galaxies which contain genes and “junk-DNA”. This junk-DNA is not coding for proteins but is supposed to have gene regulatory functions. Unlike postulated dark matter, it is proven that non-coding DNA exists, but as for dark matter, we don’t know much about it, yet. Within genomic galaxies, DNA-sequences interact via looping and protein space shuttles cruise through channels between them to mediate gene transcription. Genomic galaxies are very dynamic and the whole nucleus-universe can adapt it‘s landscape to environmental disturbances in order to adjust the genetic programme.

A whole new research field has evolved, which investigates the 4D Nucleome: the three-dimensional organisation of the nucleus-universe in space and time. As you see, a biologist can also be a kind of astronauts!

XOXO, Your Nerd

Today’s post deals with some psycho-social aspects of science based on observations which I made during the last few years. In every scientific career comes the point when you are fed up with this sh**. Actually, this happens on a regular basis:

• When you are an undergraduate, confronted with the naked truth that working more and harder doesn’t necessarily correlate with the quality of your results.
• When you are a PhD student, learning that having interesting and reproducible scientific results doesn‘t mean that a journal is ever going to publish them.
• When you are a postdoc, wondering if the decades of studying and sacrifice will ever pay off.
• When you are a group leader, realising that science will never kiss you good night or make a tea for you when you’re sick.

Working in science can be incredibly frustrating but nothing beats the feeling when an experiment finally works out (and shows what you wanted to prove), your manuscript gets accepted, or you receive the grant you applied for. I guess, beeing a researcher is more than just a job. People who are good at it, do it out of idealism, passion and the believe to change something. I have the feeling that no job could ever thrill me like science does – it can be a rollercoaster of emotions. Many people struggle on this long, stony way and not a few pay with their sanity. I also had to take a little detour to realise that I really want to do research and which perspectives it offers to me:

• the possibility to develop something from which patients could benefit some day
• the contribution to common knowledge and education
• a life full of learning
• getting to know smart and inspiring people
• a dynamic way of life, which enables you to see a lot from the world
• doing something meaningful

XOXO, Your Nerd

Faster, higher, stronger is the motto of the Olympic Games, but it is also the mission of microscopists: Faster image aquisition, higher resolution, stronger fluorescence. Times are over, when we were satisfied to see a single cell through a microscope. We want details! Even the nucleus of a cell is not enough – we want DNA! And proteins! But not just the notion of their existence as fat blobs somewhere in the cell – we want to see the architecture of DNA, we want to count proteins and we want to measure sizes! But here, resolution puts a spoke in our wheel…

Let‘s transfer the physics behind resolution into real life and go for a night walk. It’s a warm summer night and you observe a huge swarm of fireflies (Lampyridae), which all flash synchronously in order to mate. To capture this natural spectacle, you take an image…and this is what you get:

You cannot tell how many fireflies are in the swarm, neither can you precisely localize each of the animals (in our analogy, the fireflies are not buzzing around but stay on one spot…). Here, resoultion is defined as the ability to distinguish adjacent animals as separate fireflies. Resolution is limited by features of the optical instrument which you are using for the observation and the wavelength of the light your firefly emits. This is called the diffraction limit, firstly described by Erst Abbe in 1873. Tranferring this to our firefly analogy means: Two or more fireflies look like one fat firefly if they are too close to each other:

How to overcome this physical limitation to localize and count the fireflies? You cannot decrease the emitted wavelength of the fireflies (ok, with CRISPR technology you propably can) and we assume you already have the best optical instrument on the market. But the solution to this problem is rather simple: Tell the fireflies not to glow all at the same time! This can be achieved by irritating them with bright light, which makes them stop glowing immediately. Now, you just have to wait until they dare to glow again. The onset of glowing usually consists of unsynchronized blinking attempts and if you now start to take pictures every few seconds, you will be able to map every single firefly to its position in the swarm.

The same attempt is used in a super-resolution (SR) microscopy technique called single molecule localization microscopy (SMLM), which aims to overcome the diffraction limit. Structures of interest within cells are labeled with flourescent molecules. A strong laser beam is applied, in order to bleach all flourescent molecules. But the fluorescence recovers after a while, as the fireflies did, and the blinking starts. After taking images every few milliseconds for a certain period of time, computational reconstruction reveals a localization map of the fluorescent molecules and visualizes structures smaller than the diffraction limit of 250 nanometers (0,00025 mm !!!). So, we are not talking about microscopy anymore but nanoscopy!

One of the „fathers“ of this very special microscopy technique is Prof Christoph Cremer, a visionary dedicating his scientific career to the development and application of super-resolution microscopy, thereby bridging physics and biology. I was lucky that I had the possibility to work with him. I was very dissapointed to learn, that he was not honored along with the three Nobel Prize winners in 2014, who received the prize in the category of chemistry for applying super-resolution microscopy in live cells. Continue reading “How to count fireflies : the approach of super-resolution microscopy”

The blog entry of today might seem a bit esoteric dealing with the question whether there is scientific evidence for a life after death. According to recent findings in the field of genomics there is – at least a kind of. Researchers reported that some genes become actively switched on after an organism deceased, the so-called thanatotranscriptome. In their study, researchsers investigated active gene transcription in mice and fish after a postmortem period of 6 minutes up to 4 days.

Firstly, they found that beeing dead is quite stressful. Rest in piece – as if! Many genes of the stress response and cellular transport are triggered in order to fight the progressing biochemical mess and the loss of control over the putrescent body. A quite hopeless waste of remaining energy…
Secondly, being dead is similar to being ill. I guess, all the males will now feel confirmed with their I-have-a-flu-I’m-dying  attitude. Genes involved in the immune and  inflammatory response become switched on after death inducing a fight against proliferating bacteria and progressing cellular damage. Thridly, death induces death. How logical science is, right? Apoptotic mechanisms are kicked off in order to eliminate cells which are not viable anymore. Spoiler alert: that will be quite some!

So far, all of the above findings have been relatively predicatable. But another observation of this study was less straight forward to believe: Death induces life. At least in a broader sense. Some developmental genes, which are usually highly controled and most carefully orchestrated during embryogenesis, become switched on after death. These genes are involved in the formation of certain structures within the developing embryo and it is unclear why they become reactivated after having been silenced meticulously. The autors of the article ascripted this to the biochemical mess, which could be similar in development and decay.

How do these findings influence our perception of life and death? There is a rational point of view: biological processes go on automatically until cells are running out of energy and the battery is empty. Gene transcription is  epigentically controled by biochemical stimuli of the environment and after death, cells just use the remaining energy and react on the surrounding disorganisation. By this, the body automatically fights the consequences of death. Coincidentally, these environmental changes resemble the embryonic milieu and developmental genes become switched on…

A more esoteric point of view – and I do not state that this is my personal opinion – could be that the deceased body is preparing for rebirth. Many cultures and religions believe in rebirth or in a life on another level, like heaven. I personally like these ideas because it has something consolatory and it changes the perception of death. Could the genetic fight against death and the reactivation of developmental genes mark a transitory phase between the ending life and the next, soon beginning life?

The lab animals used in this study did not die because of age or disease, their bodies still had a lot of “rest energy” when they were killed. It would be interesting to see if the thanaotranscriptome of naturally deceased organisms is different from that who were actively killed. This study is clearly under debate but as long as no one proves us wrong, we can feel free to interpret these results in the way we wish…

XOXO, your Nerd

 

Zoology is the reason why I studied biology. I am fascinated by animals, their behaviour, their adaptations, and their „special features“. Unfortunately, the first thing you get to learn when you start to study zoology is that it will be hard to find a job later on. Eventhough, I chose genetics and pharma as my main subjects, zoology has still a place in my heart and so I would like to share some oddities of the animal kingdom with you.

The exciting sex life of snails

Todays issue is about the snail, a completely underestimated and overseen animal. But actually, these guys are pretty cool! I am housing 15 achat snails (Achatina fulica) and I don’t get tired of Snail-Watching. Snails are social animals and love beeing in a crowd but most likely you will encounter them alone when they are ‘on the road’. Snails love to cuddle and the smaller ones like to have a piggyback ride on the bigger ones. But the really interesting thing about snails is their secret but extravagant sex life. They are not prude and some species love to do it in a group with their flirtation taking up to 12 hours. Whenever they are not hungry or sleepy they make love…

Terrestrian snails are hermaphrodites, which means that each individual has male and female sexual organs (the absence of a conflict of sexes might explain their mutual consent about certain sex practices…). Mating strategies vary among different species but here a two virtuous exaples:

The first example comes from the grapevine snail (Helix pomatia). In their foreplay, these snails make use a sadomaso practice and shoot, cupido-like, a love-dart into the body of their partner. These darts are up to one centimeter long and consist mainly of calcium carbonate. The darts are coated with a stimulant, which increases the peristaltis in sperm-transporting tubes to increases the chances for paternity. The image does neither show the grapevie snail, I guess it’s Helix aspersa Mueller, nor is it biologically correct but it really makes me smile 😉

The second example comes from the leopard slug (Limax maximus). This guy does not only look super stylish with its leopard print, it also has an unusual mating method which could be a performance in Cirque du Soleil! When two of these hermaphordites meet, they start licking each others tail tip so that they are crawling in a circle for a while. When they are stimulated enough, they produce a long thread of mucus and hang suspended in the air from a tree branch, drip rail or other. Swinging upside-down in this position, called lamp globe, they mate. Image by wikipedia.

Worth mentioning that a mating of these hermaphrodites usually results in the mutual exchange of sperm so that both partners can become „pregnant“- But they can decide when the time is right to fertilize the eggs by their own sperm bank! Snails can store sperm up to two years until they feel that the time is right to have their babies.

I hope, I could convince you that snails are worth a closer investigation,

XOXO, your Nerd

I’m doing my PhD in epigenetics and even though this field is not new, researchers from other disciplines sometimes don’t know what epigenetics actually are. The word epi is Greek and means above in this context. Epigenetics are “add ons” to the DNA-sequence, which help to interpret the code of life in an individual way.

Within the last twenty years, we deciphered the human DNA-sequence, counted the genes coded within and finally got the feeling that “we” must be more than just our DNA-sequence. Why? Well, the human DNA is not as gene-rich as the DNA of other organisms. For example, the wild-cabbage (Brassica oleracea) has almost five times more genes than humans have, but still it didn’t win the Nobel Prize yet… It seems that size doesn’t matter – you just need to know how to use your hardware and this is where epigenetics jumps in and provides the complex software.

Every cell of our body contains the same DNA-sequence. However, we are composed of 250 different cell types. It needs to be strictly controled when genes are on or off – otherwise you would look like the blob. Every gene has a “door” and when this door is open, the RNA-Polymerase can step inside and transcribe the DNA-sequence into an RNA-sequence that is forwarded to the ribosomes to become a protein. To control when the polymerase can visit a gene, the DNA-sequence has epigenetic doormen who decide when a particular DNA-sequence can receive visitors. These epgenetic doormen use two simple mechanisms:

• No one dares to come in if barbwire is draped on your door mat! Epigenetic barbwire is composed of methyl groups, which can be attached to the DNA-sequence surrounding the entrance of the gene

• No one can find the door if it is hidden! Genes can be tightly wrapped on spools, which are called histones. These spools are saved by little locks, chemical modifications, which determine if the DNA-sequence can be decoiled from the spool to reveal the door

But there is also an epigenetic version of the morning-after pill: If the RNA-Polymerase somehow passed the doormen (bribary, inattention etc.) and the RNA-transcript is already on its way to become a protein, there is still the option to leave the dogs out to catch and degrade it. These epigenetic dogs are so-called micro RNAs which bind to their target sequences and arrange their degradation.

Through the above described mechanisms, epigenetic gimmicks determine which gene is when how active. This orchestration is massively important during the development of the embryo but as well in the adult organism. The “please do not disturb” door plates can be removed if necessary, which allows for adaptations according to environmental conditions. For example, smoking and other drugs uncover doors of genes, which are involved in dependency and addiction. Green tea is speculated to remove the barbwire from door mats of genes, which can repress the generation of tumors. Our environment, behaviour and nutrition has an impact on our genes by influencing the epigentic doormen.

XOXO, your Nerd

Without a doubt, many fascinating creatures are living on our planet. One of the most extraordinary animals I ever learned about is the naked mole-rat (Heterocephalus glaber). The naked mole is a rodent, which lives in subterranean burrows in the east African countries Somalia and Ethiopia, as well as in parts of Kenia. The naked mole is obviously naked, has a poor eye-sight and the size of a small rat (not New York City rat-size!).

On top of its bizarre appearance, its eusocial organisation is unique among mammals; like bees and ants, the naked mole community consists of a queen, responsible for producing offspring, nurses, who raise the babies, and workers, who maintain the burrow. The tasks are distributed according to the age: Teenagers take care for their siblings, adults are working in the tunnels, and the strong and older naked mole colleagues become door keepers, who protect the community from invaders, like snakes. Only three males of the community and the queen are fertile. It is speculated, that a certain stress level, maintained by the queen, suppresses the growth of the ovaries of the other females. If the queen dies, other females can “relax” and become fertile. The one, which becomes pregnant first, will be the new queen.

Even though the blind mole does not fit well in our concept of beauty, it is one step ahead of us: It features the Holy Grail of longevity! The naked mole can become 30 years old, which is ten times older than a mouse and around six times older than a rat. Researchers love the naked mole because they hope to decipher the principle of longevity by analyzing their lifestyle and metabolism. The secret is: The naked mole does not waste energy and resigns the luxury of a constant body temperature, it simply takes over the environmental temperature, which can vary between 12 °C und 32 °C. Further, the naked mole can adapt its metabolism rate according to the oxygen levels in the subterranean burrow, which can drop below 3% (air at sea level has 21 %!), if around 300 oxygen-consuming naked moles live in the badly ventilated tunnel system. The only reason the naked moles do not suffocate, is the increased oxygen binding capacity of their blood.

Longevity is not necessarily a reason to be jealous, because it comes with the cost of accumulating DNA-mutations, which can cause cancer. But not in the naked mole! On top of their long life, these guys are pretty resistant to cancer. They have highly active genes (p53 and Rb) that prevent cells from doing awkward things, like overcrowding and forming tumors. Additionally, they have a sugar called high-molecular-mass hyaluronic acid, which prevents cells from getting in contact. And here is the cherry on top (of the naked mole): they cannot feel pain. Naked moles are lacking Substance P, which is a mediator of pain.

In conclusion, naked moles are highly organized rodents ruled by a bitchy queen. Beside this drop of bitterness, they lead a long and happy life without the burden of pain and cancer. Who would not like that?

XOXO, your Nerd

You can meet Steve the blind mole here: