Super Genomics to the Rescue: Explaining and Treating Neurological Based Ailments!

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Objective

Students will analyze models of altered proteins and scripts from a genetic code to construct an explanation for the basis and treatment of a rare neurological disorder.

Big Idea

The Human Genome Project provides us access to individual genetic defects, which allows for us to better understand the molecular protein products which serve as the crux of neurological diseases.

Introduction

Lesson Background & Justification: 

              Dopamine-responsive dystonia (DRD), also known as hereditary progressive dystonia with diurnal fluctuation is a genetic movement disorder which usually manifests itself during early childhood with a variable start age. The abnormalities associated with DRD are often severe, especially in the afternoon. This condition can be considered a form of childhood "Parkinson's disease" because it is caused by an inadequate supply of dopamine to the brain. The disease however can be treated successfully with dopa therapy. Other forms of dystonia may not respond to dopa therapy, but may be treated with other therapies that can be developed through Genomic Analysis (assessment of gene fidelity) and personalized medical treatments. The culminating objectives of this lesson are to a) provide experiences for students to comprehend the behavioral and genetic basis for DRD, and b) develop an appreciation for the potential that genome sequencing for this condition as well as other health anomalies. Command of this content helps to not only iterate the concept of protein synthesis learned in lesson 1 of this unit but introduces students to more complex technologies that help us to process individual variations related to diseases like DRD and its therapeutic applications.  

Essential Prior Knowledge: Prior to experiencing this lesson, students should be familiar with the following content/concepts:

             a) Structure and Function of DNA  

             b) Gene Expression and Protein Synthesis  

             c) Enzyme Structure and Function

             d) Pedigree Analysis

Lesson Preparations:

In the effort to prepare for this lesson, I make certain that I have the following items in place: 

a) A class set of the Beery Exploration Activity, SPR Models and Mutations, SPR Metabolic Map, Beery Twin Pedigree, Richard Knox's Medical Blog and Amino Acid Side Chain Chart. (See attachments throughout the lesson)  . 

b) Student lab books.

Common Core and NGSS Standards:

HS-LS1-1- Construct an explanation based on evidence for how the structure of DNA determines the structure of proteins which carry out the essential functions of life through systems of specialized cells.

HS-LS3-2- Make and defend a claim based on evidence that inheritable genetic variations may result from: (1) new genetic combinations through meiosis, (2) viable errors occurring during replication, and/or (3) mutations caused by environmental factors.

HS-LS3-3- Apply concepts of statistics and probability to explain the variation and distribution of expressed traits in a population.

MS-LS3-1- Develop and use a model to describe why structural changes to genes (mutations) located on chromosomes may affect proteins and may result in harmful, beneficial, or neutral effects to the structure and function of the organism.

SP2- Developing and using models.  

SP4- Analyzing and interpreting data.

Standards Rationale:

     In the science classroom, students are regularly charged with tasks to collect and make sense of data from readings and investigations. What makes these science experiences powerful enough to retain however, is an instructor's ability to access, stimulate and develop students' higher order thinking capacities for cognitive growth and subsequently establishing sound learning practices. In this lesson, students learn to use images of protein models and genetic data to build complexity of thought and to build a visual reference for molecular disruptions in the molecular pathways rooted in neurons. To goal is to empower students not only use simulated research products/models to apply their scientific process skills to, but to mature these habits of mind for long term practices in the classroom when using any type of model. 

Engage

10 minutes

Section Primer: 

       Reeta and Joe Beery are a set of fraternal twins who at the age of two were diagnosed with Cerebral Palsy due to observed uncontrolled motor movement. However, and due to further observed contrasts in the twin's motor functions during the day versus night, scientists at Baylor College of Medicine, a pioneer in whole-genome sequencing of individuals, thought it was worth the efforts to examine their genes more extensively for a different diagnosis. They sequenced the genomes of the twins, their older brother, their parents and their grandparents and discovered that due to two inherited mutations for a brain based enzyme called SRP, that the twins had in fact incurred the rare condition known as  DRD or Dopa-Responsive Dystonia. Whole-genome sequencing has enabled doctors to provide the Beery twins with a simple, highly effective treatment for this condition which led them to have low levels of not just dopamine but two other neurotransmitters, serotonin and noradrenalin, key neurotransmitters for mood, emotions and motor functions. In this section of the lesson, students explore the family's journey of diagnostics and treatment in the effort to understand the significance of genomic technology in treatments foe conditions that arise from changes in the protein synthesis pathway in brain cells. 

Section Sequence:

a) Slide 1:  Direct students to explore the Beery Twins story by reading and discussing the questions on the screen. Share with students that these are the same set of twins and that we are going see their story so that we can better understand how they shifted physically and mentally as described in the classroom conversation. Play the following video: 

b) Post video, prompt students to reconstruct their previous explanations of the differences between the two images seen on the screen. Discuss as a class. 

Standards Covered:

HS-LS1-1- Construct an explanation based on evidence for how the structure of DNA determines the structure of proteins which carry out the essential functions of life through systems of specialized cells.

MS-LS3-1- Develop and use a model to describe why structural changes to genes (mutations) located on chromosomes may affect proteins and may result in harmful, beneficial, or neutral effects to the structure and function of the organism.

Explore

30 minutes

Section Primer: 

       Bioinformatics is the science of collecting and analyzing complex biological data such as genetic codes. The application of these computational techniques are used to analyse information associated with biomolecules (proteins, nucleic acids, etc.) on a large-scale, and encompasses a wide range of subject areas from structural biology, genomics to gene expression studies. In this section of the lesson, students utilize genomic data and images of biochemical models to develop an appreciation for bioinformatics as a valuable source for medical diagnostics.        

Section Sequence:

a) Slide 2:  Direct students to explore the genetic/molecular story of the Beery Twins by following the directions as presented on the screen. Between steps a and b, share with students that they will learn and understand the future of medical diagnostics and treatment via Bioinformatics. Provide students with a preliminary understanding of this field by playing the following video and discussing any questions that students may have post video.  

      

b) Slide 2: Post video and discussion, continue to read the directions aloud and give students 20 minutes to complete the tasks. Slides 3-4 can be used as visual aids for the class discussion in step e (which appears on slide 2). The answer key is attached and can be located on pages 2-4 of the document. 

 All worksheets should be taped/stapled into students lab books. 

Standards Covered:

HS-LS1-1- Construct an explanation based on evidence for how the structure of DNA determines the structure of proteins which carry out the essential functions of life through systems of specialized cells.

HS-LS3-2- Make and defend a claim based on evidence that inheritable genetic variations may result from: (1) new genetic combinations through meiosis, (2) viable errors occurring during replication, and/or (3) mutations caused by environmental factors.

MS-LS3-1- Develop and use a model to describe why structural changes to genes (mutations) located on chromosomes may affect proteins and may result in harmful, beneficial, or neutral effects to the structure and function of the organism.

SP2- Developing and using models.  

SP4- Analyzing and interpreting data.

Explain

20 minutes

Section Primer: 

        In biochemistry, metabolic pathways are series of chemical reactions occurring within a cell. In each pathway, a principal chemical is modified by a series of chemical reactions. Enzymes catalyze these reactions, and often require dietary minerals, vitamins, and other cofactors in order to function properly. Sepiapterin reductase (SPR) is an important enzyme that is functional in the metabolic pathway that makes tetrahydrobiopterin – an important cofactor used by other enzymes to make the neurotransmitters dopamine and serotonin. In this section of the lesson, students study and narrow specifics of the SPR related pathways to better understand how small chemical events in the neuron can lead to macroscopic and observable maligned behaviors in humans such as the Beery twins.        

Section Sequence:

a) Slide 5:  Share with students that they are going to take a deeper dive into the biochemistry of DRD via analyzing the dopamine and serotonin metabolic pathways in the neuron. Distinguish as you reference the image where these events in their totality represent a singular, generalized step (the synthesis step) in neurotransmission process discussed in a previous lesson. Dispense the student copies of the SRP/Nt synthesis pathway as you reference the map displayed on the screen. 

b) Direct students to explore the  pathway by following the directions and by addressing the questions on the screen. Read the directions aloud and give students 10 minutes to complete the tasks individually. (see student work attached)

c) Slide 6: Read the discussion question at the top of the slide to students. Facilitate the class discussion based on the diagram provided. (students copy of the image can be found at the bottom of their SRP/Nt synthesis pathway worksheet. 

d) Finally, instruct students to complete the question at the bottom of their sheets. Provide 5 minutes to complete this task. It is the expectation that students will provide some brief explanation of or flow chart outlining how the mutated SPR protein renders poor BH4 production which serves as a cofactor in the upstream events involved in dopamine and serotonin synthesis. 

All worksheets should be taped/stapled into students lab books. 

Standards Covered:

HS-LS3-2- Make and defend a claim based on evidence that inheritable genetic variations may result from: (1) new genetic combinations through meiosis, (2) viable errors occurring during replication, and/or (3) mutations caused by environmental factors.

MS-LS3-1- Develop and use a model to describe why structural changes to genes (mutations) located on chromosomes may affect proteins and may result in harmful, beneficial, or neutral effects to the structure and function of the organism.

SP2- Developing and using models.  

SP4- Analyzing and interpreting data.

Extend

20 minutes

Section Primer: 

       Fibromyalgia is a chronic disorder marked by widespread, unexplained pain in the muscles and joints. It's not a disease. It's a syndrome, which is a collection of symptoms that occur together. Although many people think of it as an arthritic condition due to the symptoms, it's not a type of arthritis. In this section of the lesson, students predict the probability of Joe and Reeta Beery inheriting this disorder independent of DRD, their established diagnosis and how these conditions are related.         

Section Sequence:

a) Slide 7: Share with students that they will explore a mathematical/statistical approach to understanding the Beery twin condition via a pedigree analysis. Dispense the pedigree worksheet to each student and briefly review the basic of pedigree analysis using the chart on the worksheet. 

b) Direct students to explore this pedigree by following the directions on the screen and using the Medical Blog as a vocabulary reference. Read the directions aloud, explain what the F represents on the chart and give students 15-20 minutes to complete the tasks. The answer key is attached and can be located on page 1 of the document. 

All worksheets should be taped/stapled into students lab books. 

Standards Covered:

HS-LS3-3- Apply concepts of statistics and probability to explain the variation and distribution of expressed traits in a population.

SP2- Developing and using models.  

SP4- Analyzing and interpreting data.

Evaluate

10 minutes

Section Primer:

        A Fishbone Map is a type of graphic organizer which allows students to structure ideas on a topic and make multifaceted information more manageable. It provides students with a framework for recognizing the main idea and supporting details. This kind of map can be used to analyze a complex event (eg Explaining the Dopamine Responsive Disorder), but it is flexible and can be adapted to suit the level of complexity of any text students are reading.

Section Sequence:

a) Slide 8: Direct students attention to the graphic organizer on the screen, explain how it works and the benefits of organizing medical information through cause and effect analysis. Read the directions of the evaluation aloud and give students 10 minutes to complete the tasks in their lab book before turning the assignment in. 

Standards Covered:

HS-LS1-1- Construct an explanation based on evidence for how the structure of DNA determines the structure of proteins which carry out the essential functions of life through systems of specialized cells.

HS-LS3-2- Make and defend a claim based on evidence that inheritable genetic variations may result from: (1) new genetic combinations through meiosis, (2) viable errors occurring during replication, and/or (3) mutations caused by environmental factors.

HS-LS3-3- Apply concepts of statistics and probability to explain the variation and distribution of expressed traits in a population.

MS-LS3-1- Develop and use a model to describe why structural changes to genes (mutations) located on chromosomes may affect proteins and may result in harmful, beneficial, or neutral effects to the structure and function of the organism.

SP2- Developing and using models.