Cure SMA has awarded a $140,000 research grant to Drs. Oliver Gruss and Utz Fischer at Rheinische Friedrich-Wilhelms-Universitat Bonn and Julius-Maximilians-Universitat Wurzburg in Germany to study “Regulatory cues modulating the activity of SMN in human cells.”

This projects aims to understand the details of how SMN protein works in the cell. Drs. Gruss and Fischer and their teams will analyze the impact of the SMN protein on cellular signaling networks, to understand the role SMN plays in the overall activity of the cell. Signal networks are circuits that control many aspects of a cell’s activity.

Additionally, this project systematically evaluates the mechanisms and signaling networks SMN uses to exert its function in cells. Modulation of the identified signaling networks may provide a new strategy to modulate SMN activity in intact human cells, and hence may potentially lead to new therapeutic strategies for SMA.

Meet Drs. Gruss and Fischer

Who are you?

Gruss: I am a biochemist by training. I graduated with a degree in molecular cell biology from Heidelberg University. In 2015, I became a professor of Genetics at the University of Bonn, the former capital of Germany. My laboratory works on cell division and on the transport of large molecules within the cell.

Fischer: I am a professor of biochemistry at the University of Wuerzburg in Germany. For many years my group has studied the structure and function of cellular complexes involved in gene expression. We use this knowledge to gain insight into the molecular events leading to human diseases such as SMA.

How did you first become involved with SMA research?

Gruss: SMN, whose mutations lead to SMA, has functions in different parts of cells. I was initially fascinated by the problem of how large molecules (such as SMN) can move within the different parts of the cell. Since then, I have focused on research to answer the question, “Who tells the SMN complex what to do, where to go, and when to function?”

Fischer: When I was a research scientist at the Howard Hughes Medical Institute in Philadelphia in the lab of Gideon Dreyfuss, Judy Melki’s group in Paris had just discovered the link of SMA to the SMN gene. Together with Quing Liu, a PhD student in the lab, I started to analyze the function of the SMN protein in cells. We discovered an, until then, unknown function of SMN in the building of large complexes implicated in gene expression. These studies and those made in the following years by several laboratories including ours helped us understand how SMA occurs in humans.

What is your current role in SMA research?

Gruss: We understand quite a bit about SMN’s basic functions. However, we know very little about how SMN function is coordinated with cellular programs, like when cells grow, divide, or specialize to become neuronal cells or muscle fibers, for example.

Fischer: We are currently trying to find out how the function of SMN is regulated by stimuli coming from outside and inside the cell (signaling networks). These studies are highly interesting for those who are doing basic research. However, we think they are potentially also important for the development of SMA therapies as they may uncover strategies to enhance the function of SMN.

What do you hope to learn from this research project?

We hope to learn how SMN regulation works. From that, we are convinced we can learn a lot to better understand SMA and to get innovative ideas for its therapy.

What is the significance of your study?

Our study will provide new understanding into how SMN functions and its role within cells. These insights will deepen our knowledge on the role of SMN in things such as motor neuron degeneration and therefore, will aid in therapy development.

Basic Research Funding

This grant to Drs. Gruss and Fischer is part of $1.03 million in new basic research funding that we’re currently announcing.

Basic research is the first step in our comprehensive research model. We fund basic research to investigate the biology and cause of SMA, in order to identify the most effective strategies for drug discovery. We also use this funding to develop tools that facilitate SMA research.

$140,000 to Arthur Burghes, PhD

$140,000 to Jocelyn Côté, PhD

$30,000 to Remy Bordonne, PhD

$75,000 to Jean Giacomotto, PhD

$140,000 to Christine DiDonato, PhD

$75,000 to Chris Lorson, PhD

$75,000 to Yong-Chao Ma, PhD

$75,000 to Stephen J. Kolb, PhD

$140,000 to Alberto Kornblihtt, PhD