USA: JAX ME/CFS Center and Derya Unutmaz news

Andy

Andy

Retired committee member
Derya Unatmaz of Jackson Laboratories explains the partnership between Bateman Horne Center, Jackson Laboratory, and many other collaborators as part of our exciting new research.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating illness that afflicts up to two million individuals in the US and lacks both widely accepted therapies for its management as well as meaningful understanding of its biological underpinnings.

Mounting evidence in ME/CFS patients suggests a significant role for immunological abnormalities that are thought to contribute to disease progression. More recently, the microbiome also emerged as an important potential contributor to immune perturbations. The overarching goal of our CRC is that immune cells in ME/CFS patients are programmed to respond aberrantly to environmental stimuli, or that the microbes they harbor in their gut perturb healthy immune response or metabolic activity.

To achieve our goals for advancing the mechanistic understanding of ME/CFS and identifying new strategies for patient diagnosis, prognosis, and stratification, we assembled a team of researchers and clinicians and formed an integrative center structure with highly synergistic projects.

This center structure has a Clinical Core, which will be located and managed by the Bateman Horne Center (BHC), one of the premier ME/CFS clinics in the country. The Clinical Core will then recruit and follow a cohort of early-onset ME/CFS patients for the duration of the project. Blood and fecal samples obtained at the Clinical Core will be sent to Jackson Laboratory for processing and analysis.
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Read more here https://batemanhornecenter.org/dr-derya-unutmaz-explains-collaborative-research-center-crc-bhc/
 
This is a welcome development:

"We have also engaged a range of community stakeholders, including ME/CFS patients, physicians, educators, and community activists, including #MEaction advocate Jen Brea, to participate in our Community Impact Steering Committee. Linda Avey, who is the CEO of the tracking platform Precise.ly, will help in patient clinical data tracking using online apps. Together, they will provide advice and guidance on study design, patient recruitment, and, importantly, interpretation of research results from a patient-oriented perspective, and will ensure that the JAX ME/CFS CRC remains connected to the needs of patients and physicians."
 
Really good news!
I´ve been following Derya on twitter https://twitter.com/Derya_.
I like that he, beside the focus of his research, tells that he carefully listens to ME-patients. Maybe we should invite him to the forum? I don´t mean we should take his precious time, but he might be willing to comment on some issues.
 
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I couldn't read the piece on that page because it's quite faint grey type on a white background, so I hope that Dr Unumatz won't mind me reproducing it in full here (broken up also for readability), especially since it includes a call for study participants:

Derya Unatmaz of Jackson Laboratories explains the partnership between Bateman Horne Center, Jackson Laboratory, and many other collaborators as part of our exciting new research.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating illness that afflicts up to two million individuals in the US and lacks both widely accepted therapies for its management as well as meaningful understanding of its biological underpinnings.

Mounting evidence in ME/CFS patients suggests a significant role for immunological abnormalities that are thought to contribute to disease progression. More recently, the microbiome also emerged as an important potential contributor to immune perturbations.

The overarching goal of our CRC is that immune cells in ME/CFS patients are programmed to respond aberrantly to environmental stimuli, or that the microbes they harbor in their gut perturb healthy immune response or metabolic activity.

To achieve our goals for advancing the mechanistic understanding of ME/CFS and identifying new strategies for patient diagnosis, prognosis, and stratification, we assembled a team of researchers and clinicians and formed an integrative center structure with highly synergistic projects. This center structure has a Clinical Core, which will be located and managed by the Bateman Horne Center (BHC), one of the premier ME/CFS clinics in the country.

The Clinical Core will then recruit and follow a cohort of early-onset ME/CFS patients for the duration of the project. Blood and fecal samples obtained at the Clinical Core will be sent to Jackson Laboratory for processing and analysis.

At Jackson Laboratory we will extract, interpret, and integrate meaningful data from a highly detailed profiling of the immune system, metabolomics of the blood, and high-resolution gut microbiome profiling.

These rich datasets will first be analyzed statistically to identify associations, then computationally to create a map of interactions among these biological and clinical/phenotypic components. With these analyses, we aim to create the first integrated clinical ontology to aid ME/CFS patient stratification.

An important aspect of this data generation and correlative analysis is to generate novel hypotheses that could provide clues to the disease mechanisms. Therefore, we have built in approaches in the Clinical Project to assess mechanisticlinks between immune response and metabolism, which will be further examined in detail to determine the impact of isolated bacteria strains from ME/CFS patient microbiota on inflammation.

Our multi-disciplinary investigative team combines expertise in immunobiology (Unutmaz), clinical management of (and clinical research in) ME/CFS patients (Bateman Horne Center), microbiome biology (Oh), clinical bioinformatics and biostatistics (Robinson) and Motsinger-Reif), and mass spectrometry (Yao).

They are complemented by a group of collaborators and contributors with domain expertise in high-throughput genomic profiling (Robson), microbial genomics (Adams) and Mass Spectrometry core at Jackson Laboratory managed by Dr. Ahlf Wheatcraft.

We have also engaged a range of community stakeholders, including ME/CFS patients, physicians, educators, and community activists, including #MEaction advocate Jen Brea, to participate in our Community Impact Steering Committee. Linda Avey, who is the CEO of the tracking platform Precise.ly, will help in patient clinical data tracking using online apps.

Together, they will provide advice and guidance on study design, patient recruitment, and, importantly, interpretation of research results from a patient-oriented perspective, and will ensure that the JAX ME/CFS CRC remains connected to the needs of patients and physicians.

If you would like to be screened as a willing research participant for any BHC research studies, please visit our eligibility screening survey found here.​
 
Allele said:
Can someone clarify what they mean by "early-onset"? Do they mean long-term patients, or newly-ill?
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Newly ill. But this term may be interpreted to mean different things by different researchers. For example, it could mean being ill for 3 years or less, which is how Nath said he interpreted it.
 
I very much agree with Dr K, that we need an Army of researchers studying ME.

But I personally don’t know how to get from where we are today, to reach that goal?
 
We are excited to start a new educational series on explaining our approaches in biomedical research, which we hope will be useful to the ME/CFS and chronic illness community; both to patients as well as physicians.

For our first topic, we have chosen to explain Flow Cytometry and FACS (Fluorescence-Activated Cell Sorting). This will be a mini-series of several blog articles, and is not intended to be too detailed or to serve as an academic introduction, as there are many videos and introductions online that serve that purpose. Instead, we hope to provide a sense of what Flow Cytometry is and how we use it in our research at the JAX CRC.

So why start with Flow Cytometry? For immunologists like us, this instrument is indispensable because we deal with complex mixtures of cells from blood or tissues, and flow cytometry allows us to determine the composition, frequency, and function of each of these different cell types. By identifying specific cell types, we are then able to sort these cell types into pure populations that we can use in downstream experiments or interrogations. Indeed, this technology can sort out any type of cell (even including bacterial cells), provided there is a probe you can use to specifically identify them.
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https://jaxmecfs.com/2018/01/26/scientific-concepts-flow-cytometry-overview/
 
What a great idea, for interested but non-scientific folk like me. Here's a bit that puzzles me:
Cells are first suspended in a fluid (we call it a buffer), and then passed through a narrow channel one at a time at the tremendous speed of thousands of cells per second.
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Presumably this means all the cells, despite being different types, are much the same size. If they varied much in size then the smaller ones would sometimes go along the tube side by side, and confuse results, especially if different-type small cells went along side by side. Are cells typically similar sizes? Or would they have to only do any single run with similarly sized cells, and tube to match? Or something I'm just missing?
 
Barry said:
What a great idea, for interested but non-scientific folk like me. Here's a bit that puzzles me:

Presumably this means all the cells, despite being different types, are much the same size. If they varied much in size then the smaller ones would sometimes go along the tube side by side, and confuse results, especially if different-type small cells went along side by side. Are cells typically similar sizes? Or would they have to only do any single run with similarly sized cells, and tube to match? Or something I'm just missing?
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I think the principle is that cells are diluted sufficiently that the chances of getting two passing through the light beam at the same time are very small. A pellet of a million white blood cells fills a bit more than a cubic millimetre. So a sample of 20,000 cells in 0.5ml would make them ~0.005% of the volume if my arithmetic is right. I forget the numbers we used to use but it was somewhere in this ballpark.

The cells are of slightly different sizes. Lymphocytes are generally small and barely more than a nucleus. Monocytes are a bit larger. Blasts and plasma cells can be quite a bit bigger, but they all go down the tube with plenty of room. The type of cell is traditionally identified by a combination of forward and side light scatter, one being a measure of size and the other of granularity. Taken together that tells you pretty definitely whether the cells are neutrophil granulocytes, lymphocytes or monocytes. It may well be that now that it is much easier to use several different fluorescent dyes all at once to label lineage specific surface markers that sorting is now done more or less entirely on fluorescence (CD19 for B cells, CD3 for T cells etc.) but last time I looked at data we always had scatter data as a baseline for picking out the major populations.
 
Jonathan Edwards said:
I think the principle is that cells are diluted sufficiently that the chances of getting two passing through the light beam at the same time are very small. A pellet of a million white blood cells fills a bit more than a cubic millimetre. So a sample of 20,000 cells in 0.5ml would make them ~0.005% of the volume if my arithmetic is right. I forget the numbers we used to use but it was somewhere in this ballpark.

The cells are of slightly different sizes. Lymphocytes are generally small and barely more than a nucleus. Monocytes are a bit larger. Blasts and plasma cells can be quite a bit bigger, but they all go down the tube with plenty of room. The type of cell is traditionally identified by a combination of forward and side light scatter, one being a measure of size and the other of granularity. Taken together that tells you pretty definitely whether the cells are neutrophil granulocytes, lymphocytes or monocytes. It may well be that now that it is much easier to use several different fluorescent dyes all at once to label lineage specific surface markers that sorting is now done more or less entirely on fluorescence (CD19 for B cells, CD3 for T cells etc.) but last time I looked at data we always had scatter data as a baseline for picking out the major populations.
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Yes, I agree with your arithmetic. That of course is the thing I was missing: that what goes along the tube is mostly fluid, with very spread out cells, relative to their size. That's really interesting, especially the reason for the forward and side light scatter. Thanks.
 
Blog from the Jackson Lab, an interview with Zaher Nahle of Solve ME/CFS Initiative.
For our next spotlight series, I took advantage of a recent visit to The Jackson Laboratory by Dr. Zaher Nahle, an award-winning scientist with interdisciplinary training in administration and biomedical research. Zaher is the Chief Scientific Officer (CSO) and Vice President for Research at Solve ME/CFS Initiative (SMCI), and a big proponent of ME/CFS advocacy. We talked about his path through scientific research and into patient advocacy, as well as his opinion on the ME/CFS field and where the current research is going. It was a fascinating insight into Dr. Nahle’s involvement in the field and I think the ME/CFS community will find this interview very interesting!

Hey, Zaher! Thanks so much for taking the time to meet with me. You have your Ph.D. and have previously served as a principal investigator leading scientific research. Can you tell me a little bit about yourself and your scientific background?

Thanks for meeting with me, Courtney. I did my Ph.D. at Cold Spring Harbor in Biology and Biophysics, and my thesis was on Cancer Genetics, primarily focused on programmed cell death, oncogenes, and tumor suppressors. So, I have a background in cancer as well as in genomic instability. Then I went and did Obesity and Diabetes training for my post-doctorate work. And then when I got my own lab, we worked at the intersection between tumor metabolism and genetics, and used high-throughput technologies, like microRNA and DNA genomics. My lab had projects on the diabetic heart and on cancer, and we are now finding that a lot of these are relevant to the ME/CFS field as well. So that’s my scientific background. Then I transitioned from academia and went to the Harvard Kennedy School to pursue something completely different – to get a Master’s degree in Public Administration, with a fellowship in Public Policy and Management. Then I could combine my scientific background with elements of policy design, and that’s very useful for this field.
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https://jaxmecfs.com/2018/02/06/advocate-spotlight-zaher-nahle-ph-d-m-p-a/
 
Part 2 now available
Our first Flow Cytometry educational series was focused on understanding how flow cytometry works, the types of machines used, and how data is collected. In this second part in the series, we will go over some types of flow cytometry data and how that data is interpreted.

What are the different types of flow cytometry data that are collected?

In flow cytometry, there are a few types of light that are detected by the sensors during the data acquisition. The source of light (which is non-fluorescent) can create two different paths. The first is called Forward scatter (FSC), which is formed as laser light hits a cell, and is turned into a digital version that reflects the size of the cell (Figure 1). Second, this same laser light also causes Side scatter (SSC), which is a measure of the internal complexity of the cell. For example, if there are many granules in the cell, there will be a higher SSC than for a cell with little granularity. Together, this can be very informative for separating different cell types, which can be further combined with fluorescence data, discussed below.
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https://jaxmecfs.com/2018/02/23/approaches-in-biomedical-research-flow-cytometry-part-2/
 
As part of our “People in ME/CFS Research” spotlight series, I talked with Dr. Julia Oh, who is an Assistant Professor in Microbiology at The Jackson Laboratory and the Associate Director of the JAX ME/CFS project, leading the microbiome project. Her lab investigates how our microbes contribute to our health by using diverse technologies like genomics, synthetic biology, and genome engineering to target and manipulate the microbiota.

Here is her interesting background, and more about the very exciting research directions she focuses on involving the bacteria that we cohabit with in our bodies. Keep reading for the full interview!
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So for this project, what would you hope to accomplish in the first year?

First, I want to establish the systematic cultivation pipeline of the gut microbes of the ME/CFS patients. While there are some cultivation pipelines for gut microbes known, we suspect that some of the microbes from ME/CFS patients might be unique and require different culturing conditions that we need to uncover.

So I hope that from our first set of patients, we can do the shotgun sequencing to figure out who they have, and who we need to go after for the culturomics. And establishing that pipeline, specifically for the ME/CFS patients, would be a really good goal. And if we could get an idea from the initial patient cohorts of what some of the differences are between them and healthy controls, that would be awesome. And then hopefully we can provide Derya with some hundreds of microbes for him to screen in his immune assay and start to build that immune interactome that we want to go after.
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https://jaxmecfs.com/2018/03/08/scientist-spotlight-julia-oh-phd/
 
The article is worth reading in full; it made me feel hopeful.

It seems that they have a good chance of identifying differences in gut bacteria (importantly, potentially down to strain level) between healthy people and people with ME. And then working through the possible causes and consequences of those differences.

All power to you, Dr Oh.
 
We are excited to present Dr. Lucinda (Cindy) Bateman as part of our “People in ME/CFS Research” spotlight series. Cindy is the Founder and Medical Director of the Bateman Horne Center (BHC), which is also the clinical core for the JAX ME/CFS CRC. At BHC, she cares for patients suffering from ME/CFS and Fibromyalgia, educates physicians and patients about these diseases, and develops clinical research projects with Dr. Suzanne Vernon. I recently called Cindy to ask about her journey through the ME/CFS field, and how BHC got it’s start – read on for the full interview!
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https://jaxmecfs.com/2018/03/15/clinician-spotlight-lucinda-bateman-m-d/
 
An interesting news article was just published in Nature about how the emerging tool of artificial intelligence (AI) is making it easier for scientists to study viruses. The article, written by science journalist Amy Maxmen, focuses on the difficulty of identifying the vast number of viruses within our bodies, as they are difficult to isolate or culture, and because we know so little about them that we don’t know what to even look for.

To overcome this challenge, several computational scientists have applied artificial intelligence (AI) or machine learning approaches to sequencing the bulk of the microbiome (bacteria and viruses) that inhabits human tissues. Given the complexity of this vast microbial ecosystem, AI approaches are showing great promise in decoding or identifying novel viruses among the sea of other sequences, most of which will be bacterial or host in origin. This could be an important direction in revealing important relationships or dynamics between viruses, bacteria, and human cells.
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https://jaxmecfs.com/2018/03/20/nat...ning-spots-treasure-trove-of-elusive-viruses/
 
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