MANF: no longer a mystery?

Hello everyone! My name is Amanda Sandelin, and I have conducted my traineeship co-supervised by two groups at the University of Helsinki: Mikko Airavaara’s group of BrainRepair and Samuli Ollila’s group of Biophysical Chemistry. If you do not remember what my project was all about, you can refresh your memory here: https://blogs.helsinki.fi/hilife-trainees/2022/07/07/mystery-of-manf/. 

My summer as a HiLIFE research trainee 

My master’s thesis project is about MANF or mesencephalic astrocyte-derived neurotrophic factor. As I wrote in my previous blog post; MANF is a neurotrophic factor, which has protective effects in various disease models, including Parkinson’s disease. MANF mechanisms of action and function are somewhat of a mystery, so this summer I have been working on resolving the mystery of MANF.  

To study the function and structure of MANF, I have been conducting experiments both in vitro and in silico. During my traineeship in Mikko Airavaara’s group I have been working mainly with stem cells. We have a MANF knockout human embryonic stem cell line, which I have been using to study how the loss of MANF affects cellular antioxidant defense. I have also differentiated stem cells into human dopaminergic neurons to study the role of MANF in human dopaminergic neuron development. In Samuli Ollila’s group, we combine molecular dynamics (MD) simulations with nuclear magnetic resonance (NMR) spin relaxation data to study how biomolecules, including proteins, behave. I have been simulating MANF structures in different intracellular conditions using MD simulations and compared the simulations with experimental NMR spin relaxation data to validate the methodology for studying two-domain proteins such as MANF.  

During the summer I have done a lot of cell culturing, MD simulations, immunofluorescent staining, biochemical assays and data analysis. I have had the chance to design, conduct, analyze and discuss experiments and, finally, present my work in seminars and at a conference. So, all around a science-filled summer that has resulted in some exciting results coming your way soon!  

Thank you! 

Did I solve the mystery of MANF? Maybe not yet, but the mission continues, and I have exciting results that I am now compiling in my thesis. The HiLIFE research traineeship made this project possible, and I must thank my supervisors for being open to this collaboration. Thank you to Vassileios Stratoulias, Samuli Ollila and Mikko Airavaara for guiding me as a young researcher and for allowing me to pursue my scientific curiosity.  And, of course, a big thank you to HiLIFE for giving me this opportunity to work in an inspiring research environment!  

Wishing you a cozy autumn,

Amanda Sandelin

Mystery of MANF

Hello everyone! My name is Amanda Sandelin, and I am a first-year (soon to be second-year) Master’s student in Translational Medicine. I am one of the HiLIFE Research Trainees of 2022, and I am conducting my traineeship co-supervised by two groups at the University of Helsinki; Mikko Airavaara’s group of Neuroprotection and Neurorepair and Samuli Ollila’s group of Biophysical Chemistry. My interest lies in neuroscience, but I am also interested in structural biology as a tool to help understand the details of what really is happening in our brains.  

The star of my project: MANF 

My projects revolve heavily around one protein, namely the mesencephalic astrocyte-derived neurotrophic factor or, easier said, MANF. Even though MANF is a neurotrophic factor, its characteristics differ significantly from other “traditional” neurotrophic factors. In fact, the mechanisms of action and functions of MANF are still quite a mystery. But why are we interested in this one protein? Well, what is known about MANF is that it has pleiotropic protective effects in various disease models, including Parkinson’s disease, and it is important in human development. By studying the mechanisms of MANF, we can better understand neuroprotection and identify possible new therapeutic targets. 

The next question is of course: how do we study this?  I work both in vitro and in silico, which means I work with cells and by computational models, more specifically human embryonic stem cells and molecular dynamic (MD) simulations.  Vassileios Stratoulias in our lab has established a protocol for differentiation of both wildtype and MANF knockout stem cells into dopaminergic neurons based on a previously published rigorous protocol. Using this setup, we can study the differences between wildtype and MANF knockout cells at different stages of development. In Samuli Ollila’s group, we use MD simulations and NMR to look at MANF on the molecular level and see if different conditions (such as different pH, ATP or ion concentrations) affect the structure and function of MANF.  

My first month 

I have been loving the first month of my traineeship, and I have already had a chance to learn a lot of things and immerse myself in science and research. I have been doing a lot of cell culturing, simulations, experiments, planning, analysis, and discussing and I even attended a conference, where I got to present a poster. Below are some images to really convey the amazing, science-filled month I have been enjoying. Thank you goes out to my supervisors, Vassileios Stratoulias, Samuli Ollila and Mikko Airavaara, and to everyone else in the groups for making my traineeship as great as it is. And, of course, a big thank you to HiLIFE for giving me this opportunity to experience research at its heart! 

Here you can read more about: 

Neuroprotection and neurorepair 

Biophysical chemistry 

Wishing you a lovely summer,  

AmandaSandelin