MTZ®-MPI-Award 2016: postponed by love

This year's awardees Dr. Jyoti Rao and Dr. Urs Langen marry each other on the planned date

Can you imagine a more beautiful reason to postpone an award ceremony? Probably not! On December 8^th 2016, the planned date for the annual ceremony of the MTZ-MPI-Award, Jyoti Rao and Urs Langen will celebrate their own ceremony: in New Delhi, Jyoti Rao's origin, they will marry each other.

For that reason, the award ceremony will take place at January 4^th 2016. It will start at 4 pm in the auditorium of the Max Planck Institute for Molecular Biomedicine. The awardees Dr. Jyoti Rao and Dr. Urs Langen will explain their works in short eligible presentations (in English). The laudationes will be held by PD Dr. Boris Greber and Prof. Dr. Ralf Adams. The founding couple Monika and Thomas Zimmermann will hand over the certificates. After the ceremony, at approximately 4:45 pm, there will be a reception with the opportunity to congratulate the awardees - both to the award and their wedding.

The awardees got to know each other at the Max Planck Institute for Molecular Biomedicine. Dr. Jyoti Rao finished her doctoral thesis on the differentiation of cardiac muscle cells from embryonic stem cells in the lab of PD Dr. Boris Greber. Dr. Urs Langen completed his doctoral thesis on blood vessels in bone during development in the department of Prof. Dr. Ralf Adams.

On top of these ceremonies, the MTZ®foundation celebrates its 10^th anniversary this year. With five awards of the MTZ®foundation promote the young scientific excellence that pushes forward disease research and drug development into new dimensions with groundbreaking research findings. To this extend, the MTZ®foundation has chosen highly recognized and long-standing institutes and universities and their excellent scientific junior talents. In this way, the founding couple Monika and Thomas Zimmermann wants to foster young persons in their scientific career. Ever since 2009, the MTZ®foundation distiguishes young scientists at the MPI for Molecular Biomedicine with the MTZ®-MPI-Award on a yearly basis. The award prize is endowed with 2,500 Euros.

Dr. Jyoti Rao: In two steps towards cardiac tissue

Cardiac tissue generated from pluripotent stem cells is gaining increasingly in importance. At that, scientists aim to simulate the natural processes in the early embryo. Insights from developmental studies give them clues of which genes are playing a role in these processes. Yet, it remained largely unknown how the differentiation process into cardiac tissue is controlled. Dr. Jyoti Rao from the research group of PD Dr. Boris Greber at the Max Planck Institute for Molecular Biomedicine deciphered this mechanism in human cells. Especially in the application of cardiac cells derived from patients’ cells for disease research and drug discovery, these results are of high importance.

How does an embryo generate all cell types in human body is a long-standing and fascinating question. Alike embryos, human embryonic stem cells (hESCs) are pluripotent, i.e they can differentiate into all the cell lineages in human body, such as heart muscle cells, neurons and liver cells. hESCs can be directed to differentiate into a specific cell type by manipulating the external surrounding in a culture dish based on what is known from embryological studies in other model systems. Thus, hESC differentiation protocols provide an exceptional tool to study human embryonic development in vitro.

Generation of heart muscle cells from hESCs is a stepwise process in which cells lose potency at each transition and become more specified, finally generating beating cells. The first transition from the pluripotent state to a mesoderm like state is achieved by activation of two key signaling cascades, namely BMP and WNT. Interestingly, the second transition to a more specified state requires inhibition of WNT signaling. Though one can generate beating heart muscle cells by manipulating these signaling pathways, the reason for their requirement was elusive. During her PhD studies, Dr. Jyoti Rao intensively studied the process of hESCs differentiating into heart muscle cells and analysed in detail the genome wide molecular responses triggered by the two pathways. Jyoti Rao and colleagues found out that the two pathways work in a cooperative manner and serve to block certain transcription factors. These transcription factors act as repressors of the heart muscle cell differentiation and if not blocked, they would direct the cells into alternative cell types. Her findings emphasise that the lineage commitment during embryonic development occurs in multiple bifurcating directions, each controlled by the right combination and dose of molecular signals.

This study shed light on the fundamentals of early human fetal development. An understanding of such fundamentals will drive methods to stabilize intermediate cell types, possibly with a proliferative potential. Knowledge of the appropriate molecular signals and their downstream effectors would be useful to further refine differentiation protocols to generate heart muscle cells for pharmacology, cell therapy and disease modelling.

Jyoti Rao (28) did her Bachelor degree in Zoology and her Masters degree in Genetics at the University of Delhi, India. She came to the Max Planck Institute for Molecular Biomedicine to do her PhD under the supervision of PD Dr. Boris Greber, group leader of the Human Stem Cell Pluripotency Laboratory. She was awarded several poster prizes at scientific conferences. Jyoti Rao is first author on three peer-reviewed articles – the most prominent featuring in Cell Stem Cell – and co-author also on three scientific articles. In January 2017, Jyoti Rao will start her postdoc training at the laboratory of Olivier Pourquié at the Harvard Stem Cell Institute in Boston, USA.

Dr. Urs Langen: Bone-jarring job for endothelial cells

The characterization of bone is technically difficult and, accordingly, very little is known about the exact mechanisms coupling bone growth and blood vessel formation. In a team of scientists around Ralf H. Adams of the Max Planck Institute for Molecular Biomedicine, Dr. Urs Langen has overcome these difficulties and developed staining techniques for bone specimens. Thereby, the scientists discovered a new type of blood vessels in the skeletal system that promotes bone formation. This opens new perspectives for the therapy of disorders with defective bone formation.

Blood vessels are commonly known as the distribution system for blood, which contains oxygen, nutrients and hormones and, at the same time, removes carbon dioxide, waste products and toxins from our bodies. Blood vessels are not only stiff tubes, but are a living network that is lined by endothelial cells (ECs). These cells modulate the properties of the vessel; they are highly adaptive to meet the needs of every single organ and, as recent studies show, they can also control growth, patterning and regeneration processes in the surrounding tissue.

Scientists have suspected for a long time that molecular connections link endothelial cells and bone-forming cells (osteoblasts). However, the exact crosstalk between vessels and bone growth, and the organization of the blood vessel network in the skeletal system had remained largely unknown. This knowledge gap has a technical background: bone is heavily calcified and matrix-rich so that decalcification and other processing steps are required. However, these procedures can damage the tissue and thereby obscure important details. Researchers in the department of Ralf Adams have developed methods for processing bone, in which the fine anatomical structures are retained and can be visualized.

In his PhD work, Dr. Urs Langen discovered that the architecture of bone vessels is significantly changing during development. Whereas one type of vessels supports surrounding progenitors of bone-forming cells, a second one is associated with cells of the blood-forming (hematopoietic) system. These vessel types are present in distinct locations and have distinct morphological properties, but can be also separated by flow cytometry due to expression of specific markers. With this methodology, Urs Langen discovered a third population of bone ECs present in the earliest stages of bone formation. Using state of the art RNA-sequencing methodology he unravelled that this population is even more capable of promoting osteoblastic differentiation, which is likely to facilitate rapid bone growth in the embryonic and postnatal organism. Urs Langen also demonstrated that the specification of vessel and EC subtypes in the growing bone is controlled by interactions with the extracellular matrix.

These discoveries pave the way for new kinds of therapies of bone-forming disorders; finding mechanisms to induce the formation of pro-osteogenic endothelial cells could help to stimulate bone formation in various pathological conditions.

Urs Langen (32) studied Biochemistry at the University of Tübingen in Germany. For his PhD studies, he joined the Department of Tissue Morphogenesis of Prof. Dr. Ralf Adams at the Max Planck Institute for Molecular Biomedicine. Urs Langen is author or co-author of three manuscripts that are published or under revision. He will continue his scientific career as a postdoc in the laboratory of Chenghua Gu in the Department of Neurobiology at the Harvard Medical School in Boston, USA.